Front. Oncol. Frontiers in Oncology Front. Oncol. 2234-943X Frontiers Media S.A. 10.3389/fonc.2023.1123101 Oncology Review Importance of long non-coding RNAs in the pathogenesis, diagnosis, and treatment of prostate cancer Taheri Mohammad 1 2 Badrlou Elham 3 Hussen Bashdar Mahmud 4 Kashi Amir Hossein 2 Ghafouri-Fard Soudeh 5 * Baniahmad Aria 1 * 1 Institute of Human Genetics, Jena University Hospital, Jena, Germany 2 Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan, Iraq 5 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Edited by: Yafeng Ma, Ingham Institute of Applied Medical Research, Australia

Reviewed by: Kenichi Takayama, Tokyo Metropolitan Institute of Gerontology, Japan; Nathan J. Bowen, Clark Atlanta University, United States; Lin Ye, Tongji University, China; Tao Liu, Zhongnan Hospital, Wuhan University, China

*Correspondence: Soudeh Ghafouri-Fard, s.ghafourifard@sbmu.ac.ir; Aria Baniahmad, aria.baniahmad@med.uni-jena.de

This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology

 21 03 2023 2023 13 1123101 13 12 2022 07 03 2023 Copyright © 2023 Taheri, Badrlou, Hussen, Kashi, Ghafouri-Fard and Baniahmad 2023 Taheri, Badrlou, Hussen, Kashi, Ghafouri-Fard and Baniahmad

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Long non-coding RNAs (lncRNAs) are regulatory transcripts with essential roles in the pathogenesis of almost all types of cancers, including prostate cancer. They can act as either oncogenic lncRNAs or tumor suppressor ones in prostate cancer. Small nucleolar RNA host genes are among the mostly assessed oncogenic lncRNAs in this cancer. PCA3 is an example of oncogenic lncRNAs that has been approved as a diagnostic marker in prostate cancer. A number of well-known oncogenic lncRNAs in other cancers such as DANCR, MALAT1, CCAT1, PVT1, TUG1 and NEAT1 have also been shown to act as oncogenes in prostate cancer. On the other hand, LINC00893, LINC01679, MIR22HG, RP1-59D14.5, MAGI2-AS3, NXTAR, FGF14-AS2 and ADAMTS9-AS1 are among lncRNAs that act as tumor suppressors in prostate cancer. LncRNAs can contribute to the pathogenesis of prostate cancer via modulation of androgen receptor (AR) signaling, ubiquitin–proteasome degradation process of AR or other important signaling pathways. The current review summarizes the role of lncRNAs in the evolution of prostate cancer with an especial focus on their importance in design of novel biomarker panels and therapeutic targets.

 lncRNA prostate cancer biomarker expression diagnostic Introduction

Prostate cancer is the most commonly diagnosed cancer among males being responsible for 27% of all diagnosed cases (1). It also accounts for the greatest number of deaths from cancer among men after lung cancer (1). A number of risk factors have been identified for prostate cancer among them are age, ethnicity, genetics, family history, obesity, and smoking (2, 3). Prostate cancer is developed via a multistep process, starting from prostatic intraepithelial neoplasia and being evolved to localized, advanced prostate cancer with local invasion and metastatic prostate cancer, respectively (4). The aggressiveness of prostate cancer is best described by the Gleason grading system (5). The hormone responsiveness is an important feature in this cancer resulting in tumor regression following castration (6). Therefore, androgen deprivation therapy has been suggested as the regular therapeutic regimen for prostate cancer. However, resistance to this therapeutic modality can develop (4).

Identification of the underlying cause of initiation and progression of prostate cancer is an imperative step in development of novel therapies for this kind of malignancy. Moreover, it can facilitate design of novel biomarkers for early detection of cancers. Long non-coding RNAs (lncRNAs) are promising transcripts for both purposes (7–9). These transcripts have sizes more than 200 nucleotides and are responsible for a variety of regulatory mechanisms at different levels of gene expression regulation (10). Aberrations in the expression of lncRNAs might be representative of certain phases of cancer progression, and can be used to predict early progression of cancer or induction of cancer‐related signaling pathways (11, 12). Therefore, these transcripts have attained much attention during recent years for their contribution in the pathogenesis of almost all kinds of cancers, including prostate cancer. The current review summarized the role of lncRNAs in the evolution of prostate cancer with an especial focus on their importance in design of novel biomarker panels and therapeutic targets. We used PubMed and Google Scholar databases with the key words “lncRNA” or “long non-coding RNA” and “prostate cancer”. Then, we screened the obtained articles and included the relevant ones in the manuscript. Finally, we tabulated the data obtained from these articles for the purpose of better classification of the data.

 Up-regulated lncRNAs in prostate cancer

Using quantitative real time PCR method, several lncRNAs have been shown to be over-expressed in prostate cancer tissues compared with adjacent non-cancerous tissues or benign prostate hyperplasia (BPH) samples, representing an oncogenic role for these transcripts in the progression of prostate cancer ( Table 1 ). Small nucleolar RNA host genes (SNHGs) are among the mostly assessed lncRNAs in this field. A number of well-known oncogenic lncRNAs in other cancers such as DANCR, MALAT1, CCAT1, PVT1, TUG1 and NEAT1 have also been shown to act as oncogenes in prostate cancer. For instance, DANCR has been found to contribute to the taxol resistance of in this type of cancer via modulation of miR-33b-5p/LDHA axis (44). Expression of this lncRNA has been up-regulated in serum samples of prostate cancer patients, parallel with down-regulation of miR-214-5p. Notably, DANCR expression has been correlated with PSA level, Gleason score and T stage in these patients. DANCR expression not only can be used for prostate cancer diagnosis, but also can predict poor prognosis of this type of cancer with high diagnostic value. Mechanistically, up-regulation of DANCR or down-regulation of miR-214-5p could enhance proliferation and migration, preclude apoptosis, and induce activity of TGF-β signaling (45). DANCR can also target miR-185-5p to increase expression of LIM and SH3 protein 1 promoting prostate cancer through the FAK/PI3K/AKT/GSK3β/snail axis (46).

Summary of function of up-regulated lncRNAs in prostate cancer (Official HUGO Gene Nomenclature symbols are used).

lncRNA Samples Cell lines Targets/Regulators Signaling Pathways Association with patients’ outcome Function Ref
UBE2R2-AS1 74 PTNTs RWPE-1, DU145, and PC-3 PCNA, CDK4, Cyclin D1, Bcl-2, N-cadherin, Vimentin, E-cadherin – Poor prognosis of PC patients Might serve as a biomarker for diagnosis and a promising target in case of PC therapy (13)
CASC11 66 PTNTs PC-3, DU145, 22Rv1, LNCaP, and RWPE-1 YBX1 p53 pathway – CASC11 enhances the proliferation and migratory capacity of PC cells. (14)
CASC11 29 tumor and 5 benign prostate samples PNT1a, PC3, DU145, and LNCaP miR-145 PI3K/AKT/mTOR and CASC11/miR-145/IGF1R axis – Its high expression suppresses miR-145, and activates PI3K/AKT/mTOR pathway. (15)
SNHG17 52 PTNTs RWPE-1, RV-1, PC-3, DU145, and LNCaP miR-23a SNHG17/miR-23a/OTUB1 Axis Advanced tumor stage SNHG17 may enhance the progression of PC. (14)
SNHG17 58 PTNTs LNCaP, C4-2, and HPrEC TCF1, TCF4, LEF1, c-myc, cyclin D1 and axin2 Wnt/β-catenin pathway Poor outcomes SNHG17 promotes the proliferation and viability, but suppresses apoptosis. (16)
SNHG17 36 PTNTs RWPE-1, DU145, LNCaP, VCaP, and PC-3 SNORA71B, miR-339-5p, and STAT5A SNHG17/miR-339-5p/STAT5A/SNORA71B axis Low PFS SNHG17/miR-339-5p/STAT5A modulates SNORA71B expression. (17)
SNHG17 46 patients with CRPC and 149 patients with HSPC LNCaP, C4-2, PC-3, and DU145 miR-144 and CD51 miR-144/CD51 Axis – Expression of SNHG17 was elevated in CRPC tissues and cells. (18)
SNHG16 80 PTNTs DU-145 PCa cells miR-373-3p TGF-β-R2/SMAD signaling – SNHG16 facilitates the proliferation and migration by modulating the miR-373-3p/TGF-β-R2/SMAD axis. (19)
SNHG16 52 cancer tissues and 36 normal prostate samples 22Rv1 and HPrEC GLUT1 – – SNHG16 silencing suppresses the growth of PCa cells through downregulating GLUT1. (20)
SNHG14 60 PTNTs WPMY1, LNCaP, 22RV1, PC-3, and DU145 miR-5590-3p, YY1, Cyclin D1, Bcl-2, N-cadherin, Bax, Caspase-3, and E-cadherin miR-5590-3p/YY1 axis Advanced stage and poor diagnosis SNHG14 enhances the proliferation and invasion of PCa cells through miR-5590-3p/YY1. (21)
SNHG12 85 PTNTs WPMY-1, LNCAP, DU145, and PC-3 apoptosis-related and invasion-related proteins PI3K/AKT signaling pathway – SNHG12 Silencing suppresses PCa cells proliferation. (22)
SNHG12 Blood samples from 56 PCa patients and 45 patients with BPH 22RV1, Du145, LNCaP, MDaPCa2b, and RWPE1 CCNE1 and miR-195 PI3K/AKT/mTOR pathway and miR-195/CCNE1 axis Poor prognosis SNHG12 silencing suppresses viability and induces apoptosis and autophagy of PCa cells. (23)
SNHG11 120 PCa patients and 45 cases of BPH patients 22RV1 – – Shorter OS time and biochemical recurrence-free survival SNHG11 silencing prevents the proliferation, invasion, and migration. (24)
SNHG11 30 PTNTs RWPE-1, LNCaP, C4-2, PC3, and DU145 miR-184 miR-184/IGF-1R signaling axis – SNHG11 promotes progression of PC by increasing the expression of IGF-1R. (25)
SNHG10 gene expression profiles of PC patients from TCGA database VCaP, LNCaP, 22RV1, PC3, DU145, and RWPE-1 – Immune infiltration and oxidative phosphorylation Advanced clinical parameters SNHG10 affects proliferation, migration, and invasion. (26)
SNHG9 52 PTNTs – – maintenance of cell metabolism and protein synthesis Poor prognosis SNHG9 may serves as a possible prognostic biomarker in patients with PCa. (27)
SNHG8 53 PTNTs RWPE1, LNCaP, PC3, DU145, VCap, and 22RV1 miR-384 and HOXB7 – – SNHG8 enhances the proliferation, migration and invasion of PCa cells by sponging miR-384. (28)
SNHG7 30 PTNTs PC-3 and DU-145 cells c-Myc SRSF1/c-Myc axis – SNHG7 knocking down inhibits the proliferation and glycolysis in PCa cells. (29)
SNHG7 127 PTNTs – – – Metastasis, pelvic lymph node metastasis, and TNM stage SNHG7 may serve as a possible prognostic marker and target for the treatment of PCa. (30)
SNHG6 63 PTNTs PC-3 and DU145 miR-186 SNHG6/miR-186 axis – SNHG6 was upregulated in drug-resistant PCa tissues and cells. (31)
SNHG3 30 PTNTs RWPE-1, PC-3, DU145, VCaP and LNCaP miR-1827 Wnt/AKT/mTOR pathway Poor prognosis SNHG3 may be a prognostic marker for PCa. (32)
SNHG3 40 PTNTs WPMY-1, PC-3, Du 145, LNCaP, and 22RV1 miR-152-3p SNHG3/miR-152-3p/SLC7A11 axis – Promotes proliferation, invasion, and migration of PCa cells via sponging miR-152-3p. (33)
SNHG3 26 PTNTs REPW-1, DU145, VCaP, LNCaP, C4-2B, 22RV1,and PC3 miR-214-3p SNHG3/miR-214-3p/TGF-β axis Advanced clinicopathological features and poor prognosis SNHG3 silencing suppresses bone metastasis in PCa cell. (32)
SNHG3 PTNTs LNCaP and PC-3 miR-487a-3p and TRIM25 EMT – SNHG3 sponges with miR-487a-3p, and affects migration, invasion, and EMT of PCa cells. (34)
SNHG3 – RWPE‐1, PC3, DU145, 22RV1, and LNCaP miR-577 and SMURF1 SNHG3/miR‐577/SMURF1 axis – SNHG3 affects the proliferation, migration, EMT process and apoptosis. (35)
SNHG1 Formalin fixed paraffin—embedded PCa specimens and BPH or ANTs (n=14) RWPE-1, LNCaP, 22Rv1, PC-3, DU145 E-cadherin, vimentin EMT pathway Tumor metastasis SNHG1 is a possible target for treatment of PCa. (36)
SNHG1 20 PTNTs LNCaP, PC-3, DU-145, and RWPE-1 EZH2 Wnt/β-catenin and PI3K/AKT/mTOR signaling pathway – SNHG1 affects PCa cells proliferation, apoptosis, migration, invasion, and autophagy by targeting EZH2. (37)
SNHG1 134 PTNTs PC3 and DU145 – – Aggressive malignant behavior SNHG1 may serves as a possible marker and target for treatment of PCa. (38)
SNHG1 142 PTNTs DU-145, LNCaP, 22Rv1, PC-3, and RWPE-1 miR-195-5p, E-cadherin, N-cadherin, and Vimentin EMT – SNHG1 affects PCa cells proliferation, invasion and EMT via sponging miR-195-5p. (39)
SNHG1 Normal tissues (n=318) and PCa tissues(n=92) 22Rv1 and LNCaP miR-377-3p and AKT2 SNHG1/miR-377-3p/AKT2 axis Poor overall survival rate SNHG1 sponges with miR-377-3p in PCa cells. (40)
lncHUPC1 70 PTNTs RWPE-1, LNCaP, 22RV1, DU145, and PC3 FOXA1, SDCCAG3, and miR-133b lncHUPC1/miR-133b/SDCCAG3 axis Advanced TNM stages lncHUPC1 acts as an oncogene and increases the metastasis and growth of PCa cells. (41)
MNX1-AS1 40 PTNTs LNCaP, PC-3, C4-2B, Du-145 and RWPE1 miR-2113 miR-2113/MDM2 axis Worse overall survival rates MNX1-AS1 enhances the proliferation, migration and invasion of PCa cells through miR-2113/MDM2 axis. (42)
CERS6-AS1 PTNTs DU145 and RWPE-1 miR-16-5p miR-16-5p/HMGA2 axis – Its knockdown can prevent the proliferation and migration of DU145 cells. (43)
DANCR 30 PTNTs HPrEC, RWPE-1, PC3, DU145, LN96, and OPCT-1 miR-33b-5p Glucose Metabolism – DANCR affects the proliferation, migration, and taxol resistance of PCa cells. (44)
DANCR 53 PCa patients and 47 healthy persons DU145, 22Rv1, RC-92a, PC-3M, and RWPE-1 miR-214-5p TGF-β signaling pathway Poor prognosis Elevated expression of DANCR can facilitate PC progression. (45)
DANCR 40 paired PCa tissues and ANTs 5 PCa cell lines and 1 epithelial cell line miR-185-5p FAK/PI3K/AKT/GSK3β/Snail pathway – DANCR exerts its oncogenic effects via miR-185-5p/LASP1 axis in prostate cancer. (46)
MALAT1 98 paraffin-embedded clinical specimens (3 normal samples and 95 cancer tissues) C-3, C4-2, and RWPE-1 MYBL2 MALAT1/MYBL2/mTOR Axis – Its knockdown inhibits the expression of p-mTOR. (47)
MALAT1 52 PTNTs RWPE-1, PC-3, and DU145 miR-140 and BIRC6 miR-140/BIRC6 axis Poor OS MALAT1 silencing suppresses PC progression. (48)
MALAT1 – DU145, PC3, and LNCaP miR-423-5p – Decreased survival MALAT-1 expression affects progression and survival of PCa patients. (49)
MALAT1 gene expression profiles of PC patients from TCGA database LNCaP and CWR22Rv1 miR-145 miR-145-5p-SMAD3/TGFBR2 axis Long ncRNA MALAT1 enhances the proliferation, migration, and invasion by acting as a ceRNA for miR-145. (50)
MALAT1 602 urine samples from patients with PCa and BPH – – – – MALAT-1 and PCA3 may serve as noninvasive exosomal markers for detection of PCa. (51)
PCA3
PCGEM1 26 PTNTs LNCAP, 22RV1, MDA-PCA-2B, and RWPE1 miR-129-5p PCGEM1/miR-129-5p/CDT1 axis – PCGEM1 promotes the progression of PCa through sponging miR-129-5p. (52)
PCGEM1 50 PTNTs PC-3, LNPCa, Du-145, C4-2B, and RWPE1 miR-506-3p miR-506-3p/PCGEM1/TRIAP1 axis Distant metastasis Facilitates the proliferation, invasion, and migration through sponging miR-506. (52)
NEAT1 RNA sequencing data from TCGA and GEO databases PC3 LDHA – – NEAT1 regulates LDHA expression (13)
NEAT1 130 PTNTs – – – Distant metastasis, TNM stage, and lymph nodes metastasis It has been reported that NEAT1 plays a role in the prognosis of PCa patients. (53)
NEAT1 50 PTNTs RWPE-1, PC3, P4E6, LNCaP, and DU145 miR-766-5p miR-766-5p/E2F3 axis – NEAT1 promotes progression of PCa. (54)
NEAT1 plasma of 15 PCa patients and 15 HCs and 8 FFPE tissues of PCa and ANTs – – – – NEAT1 acts as an oncogene in PCa development. (55)
NEAT1–1 FFPE or fresh-frozen hormone-naïve primary prostate cancer and bone metastatic tissues (n=60) PDXs related primary cells CYCLINL1 and CDK19 CYCLINL1/CDK19/NEAT1-1 axis Poor prognosis NEAT1 induces bone metastasis of PCa via N6-methyladenosine. (56)
LINC00624 PCa tissues – TEX10 LINC00624/TEX10/NF-κB axis Poor prognosis LINC00624 plays an oncogenic role in PCa progression. (57)
TP73-AS1 – DU-145 and PC-3 cells TP73 TP73/TP73-AS1 axis Knockdown of TP73-AS1 suppresses the proliferation of PCa cells by TP73 regulation. (58)
LINC01207 – PC-3, LNCaP, Du-145, C4-2B, and RWPE1 miR-1182 miR-1182/AKT3 axis Poor prognosis LINC01207 could directly binds with miR-1182. (59)
PCAT14 499 PCa samples and 52 adjacent normal tissue samples – – immune pathways – PCAT14 is a potential diagnosis marker in case of PCa. (60)
DLEU2 Prostate tumor tissues from TCGA database PC-3 and DU145 miR-582-5p miR-582-5p/SGK1 axis Poor prognosis High expression of DLEU2 promotes the proliferation invasion, and migration of PCa cells. (61)
BCAR4 90 PTNTs PC346, LNCap, MDAPC1 2a/b, C4-2, PC3, BPH1, and DU145 miR-15 and miR-146 GLI2 signaling – Beclin-1 expression is regulated by BCAR4 via miR-146 and miR-15 in PC cells. (62)
EIF3J-AS1 36 PTNTs PC-3, LNCaP, DU-145, and RWPE-1 MAFG – – EIF3J-AS1 induces progression of PCa through interaction with MAFG. (63)
ZEB2-AS1 PTNTs and BPH tissues – – apoptosis – No significant association was reported between the relative expression of this lncRNA and the tumor grade. (64)
HOXD-AS1 36 and 9 cases paraffin embedded PCa and BPH tissues LNCaP, PC-3, LNCaP-Bic, and LNCaP-AI miR-361-5p miR-361-5p/FOXM1 axis High volume disease Exosomal lncRNA HOXD-AS1 enhances distant metastasis. (65)
HOXA11-AS 25 PTNTs RWPE-1, PC-3, Du-145, and LNCaP miR-24-3p HOXA11-AS/miR-24-3p/JPT1 axis – HOXA11-AS1 functions as ceRNA for microRNA-24-3p, and regulates Jupiter microtubule associated homolog 1. (66)
HOXA-AS2 68 PTNTs RWPE, LNCaP, DU145 and PC3 miR-509-3p and PBX3 miR-509-3p/PBX3 axis Advanced stages Its knockdown inhibits the proliferation and migration. (67)
LncAY927529 exosomes derived from PCa patient serum BPH-1, RWPE-1, VCaP, LNCaP, DU145, and PC3 CXCL14 – – Exosomal lncRNA lncAY927529 induces proliferation and invasion of PCa cells. (66)
HCG18 – PC cells miR-370-3p miR-370-3p/DDX3X Axis – HCG18 promotes cell proliferation, invasion, and migration of PCa. (68)
LINC00115 24 PTNTs PC‐3, DU145, LNCap, 22RV2, and RWPE miR-212-5p miR-212‐5p/FZD5/Wnt/β‐catenin axis Poor prognosis LINC00115 acts as a ceRNA for miR-212-5p, and regulates FZD5 level. (69)
FOXD1-AS1 – RWPE-1, LNCap, PC3, and DU145 miR-3167 miR-3167/YWHAZ axis – FOXD1-AS1 induces malignant phenotype of PCa cells through regulating the miR-3167/YWHAZ axis. (70)
AC245100.4 PCa tissues PCa cells – STAT3/NR4A3 axis – Its silencing suppresses the tumorigenesis of PCa cells by regulating STAT3/NR4A3 axis. (62)
LNC992 Gene expression microarray data from the GEO database and cancer tissues from PCa patients PCa cells EIF4A3 – LNC992 enhances the growth and metastasis of PCa cells by regulating SOX4 expression. (71)
PCBP1-AS1 4 BPH patients, 28 HSPC patients, and 12 CRPC patients LNCaP and C4-2 cells NTD domain of AR ubiquitin–proteasome degradation process of AR Poor prognosis It has been reported that PCBP1-AS1 expression was significantly increased in CRPC. (62)
CCAT1 10 PTNTs RWPE-1, LnCaP, DU145, PC3, and 22RV1 miR-490-3p miR-490-3p/FRAT1 axis – CCAT1 enhances the proliferation, migration, and invasion of PCa cells. (72)
CCAT1 30 PTNTs RWPE-1, PC3, and DU145 miR-24-3p and FSCN1 CCAT1/miR-24-3p/FSCN1 axis – CCAT1 affects the sensitivity of PCa cells to PTX by regulating miR-24-3p and FSCN1. (73)
LOC100996425 110 PTNTs C4-2, PC‐3, 22RV1, LNCap, DU‐145, and WPMV‐1 HNF4A AMPK/mTOR signaling pathway Lower overall survival rate LOC100996425 serves as a promoter in PCa by modulating the AMPK/Mtor signaling pathway. (72)
OGFRP1 Docetaxel-sensitive (n = 70) and docetaxel-resistant (n = 72) PCa tissues PC3 and DU-145 and corresponding normal control PrEC prostate epithelial cells miR-149-5p OGFRP1/miR-149-5p/IL-6 axis Poorer overall survival It was reported that OGFRP1 was upregulated in docetaxel-resistant PC tissue samples in comparison to samples from docetaxel-sensitive patients. (74)
AATBC 86 PTNTs LNCaP, DU145, 22RV1, VCaP, PC3, and RWPE-1 miR-1245b-5p miR-1245b-5p/CASK Axis – AATBC promotes prostate cancer progression. (74)
AGAP2-AS1 – PCa cells miR-628-5p AGAP2-AS1/miR-628-5p/FOXP2 axis and WNT pathway – AGAP2-AS1 enhances PCa cell growth by modulating WNT pathway. (75)
PCAT6 CRPC tissues (n=17) and NEPC tissues (n=9) NE-like cells (PC3, DU145, and NCI-H660), LNCaP, C4-2 miR-326 PCAT6/miR-326/Hnrnpa2b1 signaling – It has been reported that PCAT6 was upregulated in NE-like cells (PC3, DU145, and NCI-H660) in comparison to androgen-sensitive LNCaP cells. (74)
PCAT6 20 PTNTs – IGF2BP2 PCAT6/IGF2BP2/IGF1R axis Poor prognosis The mentioned lncRNA was upregulated in tumor tissues with bone metastasis, and may act as a potential prognostic marker and therapeutic target in case of PCa patients with bone metastasis. (76)
CRNDE 25 PTNTs RWPE-1, LNCaP, PC3, DUL145, and VCaP miR-146a-5p – – CRNDE knocking down suppresses PC cells proliferation. (71)
LncRNA NCK1-AS1 116 PTNTs WPMY-1, PC-3, LNCaP, 22Rv1, and DU145 – – Poor prognosis lncRNA NCK1-AS1 is upregulated in PCa. its silencing can suppress PCCs proliferation. (76)
AFAP1-AS1 30 PTNTs HprEC, PC3, and DU145 miR-195-5p miR-195-5p/FKBP1A axis – AFAP1-AS1 affects the sensitivity of PCa cells to paclitaxel. (77)
AFAP1-AS1 – C4-2 cells and NE-like cells (PC3, DU145, and NCI-H660) miR-15b miR-15b/IGF1R Axis – Its expression was upregulated in castration-resistant C4-2 cells and NE-like cells, in comparison to androgen-sensitive LNCaP cells. (74)
LINC00467 22 PTNTs CaP, LNCaP, 22RV1, PC3, DU145, HrPEC, and RWPE-1 miR-494-3p M2 macrophage polarization, STAT3 pathway and miR-494-3p/STAT3 Axis – Downregulation of LINC00467 prevents migration and invasion of PCa cells. (78)
LINC01194 62 PTNTs RWPE-1, PC3, DU145, and LNCap PAX5, miR-486-5p LINC01194/miR-486-5p/GOLPH3 axis – LINC01194 serves as a tumor promotor, and enhances progression of PCa by regulating LINC01194/miR-486-5p/GOLPH3 axis. (79)
PlncRNA-1 34 PTNTs DU145 and 22Rv1 – PTEN/Akt pathway – PlncRNA-1 facilitates PCa cells proliferation, migration and invasion. (80)
MIR4435-2HG – WPMY-1, VCaP, LNCaP, DU145, and PC-3 ST8SIA1 FAK/AKT/β-catenin signaling pathway – MIR4435-2HG affects the clone formation aptitude, proliferation, invasion, and migration of PC-3 cells. (81)
PTV1 PVT1 RNA-Seq data from TCGA-PRAD database – – – Worse prognosis PTV1 is a potential diagnosis and prognosis marker in PCa. (74)
PTV1 – DU 145, PC-3, and RWPE-1 miR-15b-5p, miR-27a-3p, miR-143-3p, miR-627-5p, and NOP2 PVT1-NOP2 axis – PVT1 induces metastasis in PCa. (82)
PVT1 25 PTNTs 22RV1, DU145, RWPE-1, and 293T miR-15a-5p and KIF23 PVT1/miR-15a-5p/KIF23 axis – PVT1 modulates KIF23 via miR-15a-5p. (83)
LINC01116 – RWPE-1, DU145, PC3, LNCAP, 22RV1, and VCaP miR-744-5p miR-744-5p/UBE2L3 axis – LINC01116 enhances the proliferation, migration, invasion and EMT progress of PCa cells. (84)
PAINT tissue microarray samples from normal prostate and prostate adenocarcinoma from stages I, II, III and IV PC-3, C4-2B, 22Rv1, LNCaP-104S, and MDA-PCa-2b Slug, Vimentin, E-cadherin epithelial mesenchymal transition (EMT) and apoptosis Aggressive PCa PAINT functions as an oncogene in PCa. (85)
PTTG3P CRPC tissues and tumor tissues of patients with hormone-naive PCa androgen-independent PC cell lines and androgen-dependent PCa cell line LNCaP miR-146a-3p, PTTG1 – – PTTG3P is the ceRNA of miR-146a-3p to increase PTTG1 expression in the progression to CRPC. (86)
NORAD 74 PTNTs 22Rv1, DU145, PC-3, RWPE-1, C4-2B, HS-5, and HEK293T miR-541-3p NORAD/miR-541-3p/PKM2 axis – NORAD functions as a ceRNA of miR-541-3p to enhance the expression of PKM2, leading to development of bone metastasis in PCa. (87)
NORAD 45 PTNTs RWPE-1, PC-3, LNCap, 22RV1, and DU-145 miR-30a-5p and RAB11A miR-30a-5p/RAB11A/WNT/β-catenin pathway – NORAD facilitates the proliferation, invasion, EMT, and suppresses apoptosis of PCa cells. (88)
NORAD 30 PTNTs DU145, 22Rv1, LNCaP, and RWPE-1 miR-495-3p and TRIP13 miR-495-3p/TRIP13 axis – NORAD sponges with miR-495-3p, and increases malignant features of PCa cells. (89)
KCNQ1OT1 30 PTNTs DU145 and LNCaP miR-211-5p miR-211-5p/CHI3L1 Pathway – lncRNA KCNQ1OT1serves as a ceRNA of miR-211-5p, and upregulates CHI3L1 levels. (90)
KCNQ1OT1 30 PTNTs DU145 and PC-3 miR-15a Ras/ERK signaling – KCNQ1OT1 induces immune evasion and malignant phenotypes of PC by sponging miR-15a. (89)
BLACAT1 42 PTNTs DU145, LNCap, PC-3, and RWPE-1 miR-29a-3p and DVL3 miR-29a-3p/DVL3 Axis – BLACAT1 facilitates the proliferation, migration and invasion of PCa cells. (91)
FAM83H-AS1 8 normal prostate tissues and 20 PCa tissues PCa cells miR-15a AR signaling and miR-15a/CCNE2 Axis – FAM83H-AS1 plays an oncogenic role in PCa, and affects cell proliferation and migration. (92)
RAMS11 42 PTNTs RWPE-2, LNCap, PC3 and DU145 CBX4 – Poorer OS and DFS RAMS11 enhances the growth and metastasis of PCa cells. (86)
AC245100.4 – RWPE1, DU145, PC3, and 293T miR-145-5p and RBBP5 AC245100.4/miR-145-5p/RBBP5 axis – AC245100.4/miR-145-5p/RBBP5 ceRNA network promotes PCa cells development. (90)
Linc00662 PTNTs WPMY-1, PC-3, and DU145 – – Lymph node metastasis and distant metastasis Linc00662 affects PCa cells proliferation, migration, invasion, and apoptosis. (93)
HOTAIRM1 – PC3 and RWPE-1 Bad, Bax, Bid, and Bcl-2 Wnt pathway – HOTAIRM1 suppresses the progression of PCa. (90)
LEF1-AS1 AIPC samples from 45 patients AIPC cell lines PC3, DU145, and RWPE miR-328 Wnt/β-catenin pathway – LEF1-AS1 enhances the proliferation, migration, and invasion of AIPC cells through its angiogenic activity. (94)
PCAL7 104 PTNTs LNCaP and VCaP cells HIP1 AR signaling – PCAL7 acts as an oncogene in PCa. (95)
LINC00852 Data from TCGA database PC-3, VCaP and androgen-stimulated LNCaP cell lines epithelial-mesenchymal transition-related proteins EMT – Its upregulation promotes PC3 cells proliferation and colony formation abilities. (96)
AGAP2-AS1 50 PCa tissues and 20 BPH tissues VCaP, 22Rv1, CRL-1740, CRL-2422, PC3M, and WPMY-1 miR-195-5p and PDLIM5 – – AGAP2-AS1 affects the proliferation, migration, and invasion. (97)
LINC01006 – RWPE-1, DU145, PC3, LNCAP, and VCaP miR-34a-5p and DAAM1 LINC01006/miR-34a-5p/DAAM1 axis – LINC01006 serves as a ceRNA for miR-34a-5p, and up-regulate DAAM1 levels. (92)
MCM3AP-AS1 64 PTNTs PC-3, DU145, 22RV1, LNCaP, and WPMY-1 miR-543-3p miR-543-3p/SLC39A10/PTEN axis – MCM3AP-AS1 induces PCa cells proliferation and invasion. (98)
DLX6-AS1 20 PTNTs WPMY1, LNCap, DU145, PC-3, and VCap miR-497-5p and SNCG miR-497-5p/SNCG pathway – DLX6-AS1 exerts oncogenic role in PCa. (99)
LINC00173 124 PTNTs RWPE-1, DU145, PC-3, and LNCap miR-338-3p LINC00173/MiR-338-3p/Rab25 Axis Reduced patient survivals LINC00173 inhibits PCa cells proliferation, migration and invasion, and enhances apoptosis. (100)
NNT-AS1 – LNCaP clone FGC, VCaP, LNCaP C4-2B, PC3, and RWPE-1 miR-496 and DDIT4 NNT-AS1/miR-496/DDIT4 regulatory axis – NNT-AS1 acts as the sponge of miR-496 in PCa, and upregulates DDIT4 expression. (101)
UCA1 40 PTNTs RWPE1, 22RV1, and DU145 miR-331-3p and EIF4G1 UCA1/miR-331-3p/EIF4G1 axis – Its knockdown increases PCa cells radiosensitivity. (100)
UCA1 86 PTNTs DU145, PC-3, LNCaP, 22Rv1, and RWPE-1 miR-143 and MYO6 UCA1/miR-143/MYO6 axis – UCA1 plays an oncogenic role in prostate cancer. (102)
IDH1-AS1 20 PTNTs PC3, DU145, LNCaP, 22RV1, and WPMY-1 – IDH1-AS1-IDH1 axis – IDH1-AS1 is a potential target for treatment of PCa. (103)
CCAT2 18 PTNTs PCa, PC3, DU145, and RWPE-1 TCF7L2 and microRNA-217 Wnt/β-catenin signaling pathway – CCAT2 sponges with miR-217 to regulate TCF7L2 levels. (98)
AC245100.4 42 PTNTs RWPE-1, DU145, PC3, 22RV1, and LNCaP HSP90 NFκB signaling pathway – AC245100.4 is located in cytoplasm of PCa cells. (97)
LINC00992 60 PTNTs RWPE-1, PC3, LNCaP, DU145, and C4–2 miR-3935 and GOLM1 – – LINC00992 promotes the proliferation and migration of PCa cells, and inhibits apoptosis. (92)
LINC00675 9 primary PCa tissues and 8 CRPC tissues LNCaP-SF and LNCaP-JP human PCa cells GATA2 LINC00675/MDM2/GATA2/AR signaling axis – Expression of LINC00675 was elevated in CRPC patients. (104)
LINC01207 62 PTNTs PC-3, DU145, and RWPE-1 miR-1972 and LASP1 LINC01207/miR-1972/LASP1 axis – LINC01207 serves as a tumor promoter in PCa. (105)
MCM3AP-AS1 30 PTNTs PrSC cell, C4-2, PC-3, LNCaP, DU145, and 22Rv1 WNT5A and miR-876-5p MCM3AP-AS1/miR-876-5p/WNT5A axis Poor prognosis MCM3AP-AS1 partakes in PCa progression. (94)
LINC00920 125 prostate tumor and 10 normal tissue samples RWPE-1, LNCaP, VCaP, DU145, and PC-3 ERG and 14-3-3ϵ protein FOXO signaling pathway – LINC00920 facilitates the interaction between14-3-3ϵ protein and FOXO1. (106)
lncAMPC 32 primary PCa tissues from patients undergoing radical prostatectomy and 157 urine samples from patients with positive prostate biopsy PC-3 and RM-1 prostate cells LIF and miR-637 lncAMPC/LIF/LIFR axis – lncAMPC enhances PCa cells proliferation, viability, migration, and invasion abilities. (94)
LINC00689 80 PTNTs RWPE1, DU145, LNCaP, PC-3 and C42B miR-496 and CTNNB1 Wnt pathway Short OS time LINC00689 involves in progression of prostate cancer by increasing CTNNB1 levels. (107)
LINC00473 – DU145, LNCaP, PC-3, and P69 miR-195-5p and SEPT2 JAK-STAT3 signaling pathway and miR-195-5p/SEPT2 axis – LINC00473 partakes in PCa cell proliferation through JAK-STAT3 signaling pathway. (108)
FAM66C Prostate carcinoma dataset of the TCGA DU145, LNCaP, PC-3, PC-3M-IE8, and WPMY-1 – EGFR-ERK signaling, proteasome and lysosome pathways Shorter OS Its upregulation induces cell growth in PCa cells. (109)
OGFRP1 57 PTNTs PC-3, DU-145, C4-2, VCAP, RWPE-1, and 293T miR-124-3p and SARM1 – TNM stages III and IV and perineural invasion OGFRP1 sponges with miR-124-3p, and induces PCa cells growth. (110)
TUG1 39 PTNTs RWPE-1, PC-3, and DU145 miR-496 miR-496/Wnt/β-catenin pathway – TUG1 sponges with miR-496, thus suppressing expression of miR-496. (111)
TUG1 50 PTNTs WPMY-1, LNCaP, 22RV1,PC-3, and DU145 miR-139-5p and SMC1A TUG1/miR-139-5p/SMC1A axis Lower survival rate and poor prognosis TUG1 partakes in prostate cancer radio-sensitivity. (92)
TUG1 – RWPE1, PC-3, and DU145 Nrf2, HO-1, FTH1, and NQO1 Nrf2 signaling axis – TUG1 exerts oncogenic role in PCa cells. (111)
TUG1 30 PTNTs PC-3, DU145, and RWPE-1 miR-128-3p and YES1 miR-128-3p/YES1 axis Poor prognosis TUG1 may serves as a potential target for treatment of prostate cancer patients. (112)
SOX2-OT 27 PTNTs NPrEC. LNCaP, and DU145 HMGB3 and miR-452-5p miR-452-5p/HMGB3 Axis and Wnt/β-Catenin Pathway lymph metastasis, and TNM stages SOX2-OT sponges with miR-452-5p, and modulates HMGB3 levels, and regulates the Wnt/b-catenin signaling pathway. (105)
LINC00665 41 PTNTs LNCaP, PC-3, DU-145, 22RV1, and RWPE-1 miR-1224-5p and SND1 miR-1224-5p/SND1 pathway Poor prognosis Its knockdown inhibits the migration and invasion of PCa cells. (113)
ZEB1-AS1 30 PTNTs RWPE-1, DU145, and LNCaP miR-342-3p and CUL4B PI3K/AKT/mTOR signal pathway and miR-342-3p/CUL4B axis – ZEB1-AS1 silencing represses PCa cells proliferation, migration, and invasion. (110)
UNC5B-AS1 50 PTNTs PC-3, DU-145, 22RV1, Lncap and WPMY-1 caspase-9 – Distant metastasis and advanced pathological stage UNC5B-AS1 regulates the expression of Caspase-9 in PCa tissues and cell lines. (114)
CRNDE 64 PTNTs PC3 and 22RV1 miR-101 miR-101/Rap1A axis Poor outcomes Increased CRNDE levels induces the proliferation, migration, and invasion of Pca cells. (110)
ZFAS1 30 PTNTs RWPE-1, PC3, DU145, 22RV1, and LNCAP miR-135a-5p – – ZFAS1 silencing suppresses PCa cell proliferation, invasion, and metastasis through modulating miR-135a-5p. (115)
PRRT3-AS1 GSE55945 and GSE46602 datasets DU145, LNCaP, PC3, IA8, IF11, and RWPE-1 PPARγ mTOR signalling pathway – Its silencing suppresses the mTOR signaling pathway. (116)
LINC00673 48 PTNTs PC3, LNCap, DU145, paclitaxel-resistant cell line (DU145/pr), and RWPE-1 KLF4 – TNM stage and LNM LINC00673 modulates KLF4. (117)
VPS9D1-AS1 PRAD tissues from TCGA database RWPE-1, DU145, VCaP, PC-3, and LNCaP miR-4739, ZEB1 and MEF2D miR-4739/MEF2D axis – VPS9D1-AS1 enhances the proliferation, migration, and invasion. (116)
NCK1-AS1 Blood samples from 60 patients with PCa, 58 patients with BPH, and 60 healthy males DU145, 22Rv1, and RWPE-1 TGF-β1 TGF-β pathway – Expression of NCK1-AS1 was elevated in plasma of PC patients in comparison to patients with BPH and healthy controls. (118)
VIM-AS1 88 PCa and 31 normal prostate tissue samples RWPE-1, LNCaP, DU145, 22RV1, and PC3 vimentin EMT Large tumor size, metastasis and advanced TNM stage Expression of VIM-AS1 affects the migration and invasion of PCa cells. (119)
MALAT1 10 pairs of PCa tissues and ANTs DU145 and 22RV1 METTL3 PI3K/AKT signaling pathway Tumor recurrence Elevated level of MALAT1 results in tumor recurrence in PCa patients. (120)
MAFG-AS1 495 PCa tissues and 50 ANTs PC-3 and DU145 ribosome-related genes ribosome and DNA replication pathways Poor prognosis MAFG-AS1 silencing suppresses the proliferation, migration, and invasion of PCa CELLS. (121)
lncRNA AC008972.1 PCa tissues PC3 and LNCaP miR-143-3p lncRNA AC008972.1/miR-143-3p/TAOK2 axis Low OS AC008972.1 plays an oncogenic role in the progression of PCa and may serve as a possible therapeutic target in case of PCa. (122)

BPH, benign prostate hyperplasia; PCa, prostate cancer; PTNTs, paired tumor-non-tumor tissues; HSPC, hormone-sensitive prostate cancer; CRPC, castration-resistant prostate cancer.

In addition, MALAT1 has been found to regulate glucose metabolism through modulation of MYBL2/mTOR axis (47). Moreover, in vitro and in vivo studies have shown the importance of MALAT1/miR-140/BIRC6 axis in the progression of prostate cancer (48). In fact, MALAT1 acts as a molecular sponge for miR-140 to enhance expression of the anti-apoptotic protein BIRC6 (48). In turn, expression and activity of MALAT1 have been shown to be regulated by miR-423-5p, a miRNA that impedes activity of MALAT1 in enhancement of proliferation, migration, and invasiveness of prostate cancer cells (49). Most importantly, up-regulation of miR-423-5p could enhance survival and decrease metastasis formation in a xenograft model of prostate cancer (49). In addition, MALAT1 has a possible diagnostic value in prostate cancer. Expression levels of PCA3 and MALAT1 in urinary exosomes have been shown to be superior to the currently used clinical parameters in detection of prostate cancer, particularly high-grade ones (51).

NEAT1 has also been shown to regulate aerobic glycolysis to affect tumor immunosurveillance by T cells in this type of cancer (13). It can also promote progression of prostate cancer through modulation of miR-766-5p/E2F3 axis (54).

CTBP1-AS is reported as the antisense-RNA transcript positively regulated by androgen and promotes castration-resistant prostate cancer tumor growth (123). This lncRNA is localized in the nucleus and its levels are mostly increased in prostate cancer. It enhances both hormone-dependent and castration-resistant tumor growth. From a mechanistical point of view, CTBP1-AS suppresses the expression of CTBP1 through recruitment of PSF and histone deacetylases. It also exerts androgen-dependent function through inhibition of tumor-suppressor genes and enhancement of cell cycle progression (123).

Epigenetic repression of AR corepressor is an important mechanism for AR activation. ARLNC1 is also regulated by androgen and upregulates AR mRNA stability by binding to the 3’-UTR. In line with this, ARLNC1 silencing leads to inhibition of AR expression and suppression of AR signaling as well as of growth of prostate cancer. In fact, ARLNC1 has a role in the preservation of a positive feedback loop that induces AR signaling in the course of prostate cancer progression (124). In addition to these lncRNAs, several CRPC-specific AR-regulated lncRNAs are important for overexpression of AR and its variant. These AR-regulated lncRNAs are over-expressed in CRPC tissues. An experiment in these cells has shown that knock-down of PRKAG2-AS1 and HOXC-AS1 leads to suppression of CRPC tumor growth in addition to inhibition of expression of AR and AR variant. Mechanistically, PRKAG2-AS1 modulates the subcellular localization of the splicing factor, U2AF2. This splicing factor is involved in the AR splicing system (125).

SChLAP1 is another up-regulated lncRNA in prostate cancer whose up-regulation is associated with poor patient outcomes, such as metastases and prostate cancer specific mortality. It has a critical role in invasiveness and metastasis. Functionally, SChLAP1 influences the localization and regulatory function of the SWI/SNF complex (126).

PCAT-1 is another up-regulated lncRNA in prostate cancer which enhances cell proliferation through cMyc. Mechanistically, PCAT-1–associated proliferation depends on stabilization of cMyc protein. Moreover, cMyc has an essential role in a number of PCAT-1–induced expression alterations (127).

HOTAIR as regarded as an AR-repressed lncRNA is upregulated after androgen deprivation therapy and in CRPC. Mechanistically, HOTAIR binds to the AR protein to inhibit its interactions with the E3 ubiquitin ligase MDM2, thus suppressing AR ubiquitination and its degradation. Therefore, HOTAIR induces androgen-independent AR activation and drives the AR-mediated transcriptional program in the absence of androgen (128). Another study has shown that NEAT1 induces oncogenic growth in prostate tissue through changing the epigenetic marks in the target genes promoters to induce their transcription (129). Moreover, PCGEM1 and PRNCR1 bind to AR and enhance selective looping of AR-bound enhancers to target gene promoters (130). Similarly, SOCS2-AS1 interacts with AR for co-factor interaction (131).

The importance of other up-regulated lncRNAs in prostate cancer is summarized in Figure 1 and Table 1 .

Upregulation of oncogenic lncRNAs and their relation with signaling pathways in prostate cancer. PI3K/AKT/mTOR, Wnt/β-catenin, RAS/RAF, JAK and TGF-β pathways are regulated by oncogenic lncRNAs in prostate cancer.

 Down-regulated lncRNAs in prostate cancer

A number of other lncRNAs have been found to act as tumor suppressors in prostate cancer ( Table 2 ). For instance, LINC00893 can inhibit progression of this type of cancer via modulation of miR-3173-5p/SOCS3/JAK2/STAT3 axis (132). Similarly, the sponging effect of LINC01679 on miR-3150a-3p has a role in inhibition of progression of prostate cancer through affecting expression of SLC17A9 (133). MIR22HG is another tumor suppressor lncRNA that acts as a molecular sponge for miR-9-3p (134). The tumor suppressor role of RP1-59D14.5 in prostate cancer is mediated through activation of the Hippo signaling and enhancement of autophagy (135). Moreover, MAGI2-AS3 has been shown to inactivate STAT3 signaling and suppress proliferation of prostate cancer cells through acting as a miR-424-5p sponge (136). NXTAR is another tumor suppressor lncRNA that modulates expression of androgen receptor (AR) and resistance to enzalutamide (137). Totally, the number of identified tumor suppressor lncRNAs in prostate cancer is far below that of oncogenic lncRNAs ( Figure 2 ). Table 2 summarizes the information about tumor suppressor lncRNAs in prostate cancer.

Summary of function of down-regulated lncRNAs in prostate cancer (Official HUGO Gene Nomenclature symbols are used).

lncRNA Samples Cell line Targets/Regulators Signaling Pathways Association with patients’ outcome Function Ref
LINC00893 66 PTNTs PC-3, DU145, VCaP, LNCaP, and RWPE-1 miR-3173-5p miR-3173-5p/SOCS3/JAK2/STAT3 axis Poorer overall survival rate LINC00893 is a tumor-suppressor in PCa. (132)
LINC01679 55 PTNTs RWPE-2, DU145, PC-3, LNCaP, C4-2B, and 22RV1 miR-3150a-3p miR-3150a-3p/SLC17A9 axis Poor survival LINC01679 serves as a molecular sponge for miR-3150a-3p in prostate cancer. (133)
MIR22HG – RWPE-2, 22Rv1, DU145, LNCaP, and PC3 miR-9-3p MIR22HG/miR-9-3p axis – MIR22HG reduces cell proliferation and enhances apoptosis in DU145 cells. (134)
RP1-59D14.5 – LNCaP, PC3, DU145, and RWPE-1 miR-147a/LATS1/2 axis Hippo signaling pathway – RP1-59D14.5 acts as a ceRNA for miR-147a, and regulates large tumor suppressor kinase 1/2. (135)
MAGI2-AS3 109 PTNTs WPMY-1, PC-3 and DU145 miR-424-5p and COP1 STAT signaling – Elevated expression of MAGI2-AS3 suppresses PCa cell proliferation. (136)
NXTAR PTNTs RWPE-1, 22Rv1, LNCaP, VCaP, PC3, LAPC4, and C4-2B – ACK1/AR signaling – NXTAR expression was lower in various AR-positive PCa cell lines in comparison to normal prostate cells. (137)
FGF14-AS2 Gene expression profiles of PC patients from TCGA database RWPE-1, DU145, PC‐3, PC‐3 M, and LNCaP miR-96-5p iR-96-5p/AJAP1 axis – lncRNA FGF14-AS2 affects proliferation and metastasis of PCa cells by regulating iR-96-5p/AJAP1 axis. (138)
ADAMTS9-AS1 68 PTNTs PC3, DU145 and Normal human prostate epithelial cells miR-142-5p miR-142-5p/CCND1 axis TNM stage and perineural invasion ADAMTS9-AS1 suppresses the progression of PCa by affecting the miR-142-5p/CCND1 axis. (139)
MBNL1-AS1 Tissues of prostate adenocarcinoma (PARD) and normal tissues LAPC4, LNCaP, DU145, C4-2B, and RWPE-1 miR-181a-5p PTEN/PI3K/AKT/mTOR pathway – MBNL1-AS1 regulates PTEN by sequestering miR-181a-5p. (140)
LINC00641 23 PTNTs PC-3, C42B, LNCaP, and RWPE-1 VGLL4 and miR-365a-3p miR-365a-3p/VGLL4 axis Lower survival rate LINC00641 is a tumor suppressor lncRNA in PCa, and modulates miR-365a-3p/VGLL4 axis. (141)
PGM5-AS1 PCa-related microarray datasets (GSE3325 and GSE30994) PC-3, LNCap, 22RV1, DU145, and RWPE-1 miR-587, GDF10 PGM5-AS1/miR-587/GDF10 axis – PGM5-AS1 acts as a ceRNA for miR-587, and upregulates GDF10 levels. (142)
GAS5 51 PTNTs DU145, LNCaP, and WPMY-1 miR-320a and RAB21 miR-320a/RAB21 axis – Its upregulation inhibits viability and migration of PCa cells. (143)
GAS5 – – – GAS5/miR-18a-5p/serine/threonine kinase 4 – GAS5 functions as a tumor suppressor, and inhibits the metastasis and proliferation of paclitaxel-resistant PCa cells (121)
LINC00261 83 PTNTs LNCap, PC-3, DU145, 22Rv1, ARCaP, and RWPE-1 DKK3 and GATA6 LINC00261/GATA6/DKK3 axis – LINC00261 modulates DKK3. (144)
EMX2OS 25 PTNTs LNCaP, DU145, PC3, RWPE-1 and HEK293A FUS and TCF12 cGMP-PKG pathway – EMX2OS suppresses tumor growth in vivo. (145)
LINC00844 62 PTNTs 22Rv1, VCaP, LNCaP, Du145, PC-3, and RWPE‐1 GSTP1 and EBF1 LINC00844/EBF1/GSTP1 axis – LINC00844 may serve as a potential target for PCa treatment. (146)
Erbb4-IR 60 PTNTs 22Rv1 and DU145 miR-21 – Poor survival Erbb4-IR mediates the proliferation and apoptosis of PCa cells through miR-21. (147)
MIR22HG 9 normal and 13 prostate tumor sample LNCaP, WPMY-1, PC-3 and C4-2B – TNF, Cytokine-cytokine receptor interaction, MAPK, NF-κB, Jak-STAT, p53, NOD-like receptor signaling, Toll-like receptor, Cytosolic DNA-sensing, and PI3K-Akt T stage MIR22HG may acts as a potential biomarker in case of prostate cancer diagnosis. (148)
FER1L4 78 PTNTs PC-3, LNCaP, DU145, and RWPE-1 FBXW7 and miR-92a-3p ER1L4/miR-92a-3p/FBXW7 axis and key signaling pathway – FER1L4 inhibits cell proliferation and promotes cell apoptosis by increasing expression of FBXW7 in PCa cells. (145)
BLACAT1 25 PTNTs PC3, DU145, and RWPE-1 DNMT1, HDAC1, EZH2, MDM2 and miR-361 – – Its silencing reduces the growth of PCa cells, and induces cell death. (102)
LINC00908 55 PTNTs VCaP, LNCaP, DU-145, PC-3, and RWPE-1 miR-483-5p and TSPYL5 LINC00908/miR-483-5p/TSPYL5 axis – LINC00908 sponges with miR-483-5p and suppresses PCa progression. (149)
DGCR5 64 PTNTs 22Rv1 and DU145 TGF-β1 – Poor survival High expression of DGCR5 reduces PCa cells stemness. (150)
MAGI2-AS3 PCa serum samples LNCaP and PC3 cells miR-142-3p – – High level of MAGI2-AS3 inhibits proliferation, migration, and invasion of PCa cells. (151)

PCa, prostate cancer; PTNTs, paired tumor-non-tumor tissues.

A synopsis of the known roles of lncRNA tumor suppressors in prostate cancer. Several lncRNAs can reduce cell proliferation and invasiveness of prostate cancer cells, particularly through sponging oncogenic miRNAs.

 Contribution of lncRNAs variants in prostate cancer

Contribution of single nucleotide polymorphisms (SNPs) within GAS5, POLR2E, MEG3, MALAT1 and HOTAIR in the risk of prostate cancer has been assessed in different ethnic groups ( Table 3 ). Three SNPs within GAS5 have been the subject of these investigations. First, rs145204276 (delCAAGG) is located within the promoter region of GAS5. Compared with subjects carrying ins/ins genotype, cases with ins/del or del/del genotype of this polymorphism have shown decreased risk of pathological lymph node metastasis (152). The rs17359906 in GAS5 is another SNP whose A allele has been shown to be a risk allele for prostate cancer. Similarly, A allele of rs1951625 SNP within GAS5 has been associated with higher risk of this cancer. Both rs17359906 G > A and rs1951625 G > A have been associated with high plasma level of PSA. Most importantly, the recurrence-free survival of patients with prostate cancer has been lowest in patients having AA genotype of rs17359906 and highest in those having GG genotype. Similar findings have been reported for the rs1951625 (153).

Contribution of lncRNAs SNPs in prostate cancer.

Gene Polymorphism Samples Population Association Ref
GAS5 rs145204276 Blood samples from 579 PCa patients and 579 healthy controls Taiwan Compared with subjects carrying ins/ins genotype, cases with ins/del or del/del genotype of this polymorphism demonstrate decreased risk of pathological lymph node metastasis. (152)
GAS5 rs17359906 G > A Blood samples from 218 PCa patients and 220 healthy controls Chinese Han The mentioned SNP is correlated with increased plasma PSA levels. (153)
rs1951625 G > A Subjects who carry the A allele of this polymorphism show a significantly higher risk of PCa compared to those who carry the G allele.
POLR2E rs3787016 5 eligible case-control studies including 5472 cases and 6145 controls – Genotypes carrying the T allele of the mentioned polymorphism show an increased risk for PCa. (154)
MEG3 rs11627993 C>T Blood samples from 65 prostate cancer patients and 200 healthy subjects Chinese Han No statistically significant results. (155)
rs7158663 A>G
MALAT1 rs619586 Blood samples from 579 patients with prostate cancer Taiwan Cases with G allele of this polymorphism have an elevated risk of being in an advanced Gleason grade group. (156)
rs3200401 No statistically significant results.
rs1194338 Subjects who carry at least one polymorphic A allele of the mentioned SNP are positively associated with node-positive PCa.
HOTAIR rs12826786 Peripheral blood samples of 128 PCa patients, 143 BPH patients and 250 normal males Iranian Mentioned polymorphism is associated with PCa risk in co-dominant and recessive models. (157)
rs1899663 T allele of this SNP is associated with BPH risk.
rs4759314 No statistically significant results.

A systematic review and meta-analysis of 5 studies on the role of rs3787016 within POLR2E has revealed increased susceptibility to prostate cancer for carriers of T allele in all genotype models (154). The results of other studies on contribution of lncRNAs SNPs in prostate cancer are shown in Table 3 .

 Importance of lncRNAs as prognostic factors in prostate cancer

Several studies have indicated the importance of dysregulation of lncRNAs in the prediction of survival times of patients with prostate cancer ( Table 4 ). Overall, up-regulation of oncogenic lncRNAs is predictive of lower survival time of patients in terms of overall survival or progression-free survival. For tumor suppressor lncRNAs, an opposite effect has been seen.

Importance of lncRNAs as prognostic factors in prostate cancer (PTNTs, paired tumor-non-tumor tissues; PCa, prostate cancer; OS, overall survival; PFS, progression-free survival).

lncRNA Sample number Kaplan-Meier analysis Univariate cox regression Multivariate cox regression Ref
UBE2R2-AS1 74 PTNTs Its high expression is associated with poorer survival rate. – Gleason score and expression of UBE2R2-AS1 are independent prognostic factors for OS of PC patients. (13)
SNHG17 52 PTNTs Its high expression is associated with poor BCR-free survival. Over expression of SNHG17 is associated with poor OS in PC patients. Its expression is an independent prognostic factor for OS in patients with PC. (14)
LINC00893 66 PTNTs Its low expression is correlated with poorer OS. – – (132)
LINC01679 55 PTNTs Its low expression is correlated with reduction in DFS. – – (133)
SNHG3 30 PTNTs Its high expression is associated with shorter OS time. – – (32)
lncHUPC1 70 PTNTs High lncHUPC1 expression is correlated with poor PFS. – – (41)
MNX1-AS1 40 PTNTs Its high expression is correlated with worse OS rates. – – (42)
NEAT1 50 PTNTs Its high expression is associated with lower survival rate. – – (54)
SNHG3 50 PTNTs Its upregulation is associated with shorter OS and BMFS. Its high expression is an independent risk factor for death and progression in patients with PCa. (32)
DLEU2 Prostate tumor tissues from TCGA database Its high expression is correlated with lower survival rate. Its upregulation is associated with a poor progression-free interval. Its upregulation is independently associated with a poor progression-free interval. (61)
HOXD-AS1 36 PCa and 9 BPH cases Its high expression is associated with shorter PSA. Serum exosomal HOXD-AS1 in conjunction with tumor stage is a prognostic factor for PRFS. Serum exosomal HOXD-AS1 is an independent prognostic factor for PFS (65)
SNHG10 gene expression profiles of PCa patients from TCGA database Its high expression is associated with poor PFS of PC patients. Elevated expression of SNHG10, T stage, N stage, Gleason score, primary therapy outcome, residual tumor, and PSA were associated with PFS in patients with PCa. SNHG10 is an independent prognostic factor for PFS in PC patients (26)
PCBP1-AS1 4 BPH patients, 28 HSPC patients, and 12 CRPC patients Its high expression indicates a poor prognosis for PCa patients. – – (62)
LOC100996425 110 PTNTs Its elevated expression is associated with a lower OS rate of PCa patients. – – (72)
OGFRP1 70 docetaxel-sensitive and 72 docetaxel-resistant PCa tissues Its higher expression in docetaxel-resistant patients is associated with poorer OS relative to the docetaxel-sensitive patients. – – (74)
DANCR 53 PTNTs Its high expression is associated with lower OS in PCa patients. Its expression might be prognostic indicators of PC patients. DANCR is an independent prognostic indicator for PCa. (45)
SNHG17 53 PTNTs Its high expression is associated with poor OS time. – – (16)
PVT1 RNA-Seq data from TCGA-PRAD database Its high expression is associated with poor vital survival rates. Its expression is associated with OS and relapse-free survival. Its high expression is an independent prognostic factor for poor OS and poor relapse-free survival in PCa. (74)
NORAD 74 PTNTs Its high expression is positively associated with OS of patients with PCa. – – (87)
ADAMTS9-AS1 68 PTNTs Its low expression is associated with TNM stage and perineural invasion. – – (139)
RAMS11 42 PTNTs Its upregulation is correlated with poorer OS and DFS. – – (86)
SNHG9 495 PCa tissues and 52 adjacent prostate tissues Its high expression is associated with poor prognosis. Its expression level is associated with poorer PFS. Its expression is independently associated with PFS in PCa patients. (27)
LINC00641 23 PTNTs Its low expression is associated with lower survival rate. – – (141)
Discussion

Several lncRNAs have been shown to contribute to the pathogenesis of prostate cancer via modulation of AR signaling, ubiquitin–proteasome degradation process of AR or other important signaling pathways. Some of them such as PCA3 are highly specific for this kind of cancer, representing an appropriate biomarker for prostate cancer (151). Others might be over-/under-expressed in a variatey of cancers, being therapeutic targets for a wide range of human malignnacies. The observed differences in expression of some lncRNAs between castration-resistant prostate cancer and androgen deprivation therapy-responsive cases imply the importance of these transcripts in defining response of patients to this therapeutic modality and represent these transcripts as targets for management of resistance to this therapy.

Although numerous prostate cancer-specific or prostate cancer-associated lncRNAs have been recognized, few lncRNAs have been verified in independent patient cohorts or approved for using in clinical settings. The most important milestone in the field of lncRNA research is probably approval of urinary PCA3 as a biomarker for detection of prostate cancer by the United States Food and Drug Administration (158). This lncRNA is a promising factor for urine test for prostate cancer and has a superior performance compared with PSA in urinary detection of this disorder. Further reseraches are needed to find other appropriate lncRNA biomarkers for this kind of cancer.

LncRNA profiles can also been used to identify prostae cancer patients that benefit from radiotherapy. For instance, UCA1 has beens shwon to mediate radiosensitivity in prostate cancer cell lines and therefore might be a marker to predict response to radiotherapy in these patients. This lncRNA affects radiosensitivity through influencing cell cycle progression (159).

The importance of lncRNAs in the mediation of cell proliferation, invasiveness and metastasis has potentiated them as therapeutic targets for prostate cancer. The results of animal studies have been promising particularly for some AR-regulated lncRNAs. However, clinical studies are missing in this field.

Notably, LncRNAs are also involved in drug resistance in prostate cancer cells, thus they are proper candidates for therapeutic targeting (160). For instance, HORAS5 up-regulation can trigger taxane resistance in CRPC cells through upregulation of BCL2A1. HORAS5 silencing can reduce resistance of prostate cancer cells to cabazitaxel and enhance the efficacy of chemotherapy (161).

PI3K/AKT/mTOR, Wnt/β-catenin, TGF-β, p53, FAK/PI3K/AKT/GSK3β/Snail, STAT3, FAK/AKT/β catenin, Ras/ERK, NF-κB and FOXO signaling pathways are among signaling pathways that are modulated by lncRNAs in the context of prostate cancer. Moreover, several lncRNAs have been shown to act as molecular sponges for miRNAs to regulated expression of miRNA targets. miR-145/IGF1R, miR-23a/OTUB1, miR-339-5p/STAT5A/SNORA71B, miR-144/CD51, miR-5590-3p/YY1, miR-195/CCNE1, miR-184/IGF, miR-152-3p/SLC7A11, miR-214-3p/TGF-β, miR‐577/SMURF1, miR-377-3p/AKT2, miR-133b/SDCCAG3, miR-2113/MDM2, miR-16-5p/HMGA2, miR-140/BIRC6 axis, miR-145-5p-SMAD3/TGFBR2, miR-129-5p/CDT1 axis, miR-766-5p/E2F3, miR-1182/AKT3, miR-582-5p/SGK1, miR-361-5p/FOXM1, miR-24-3p/JPT1, miR-509-3p/PBX3, miR-370-3p/DDX3X, miR-212‐5p/FZD5, miR-3167/YWHAZ, miR-490-3p/FRAT1, miR-24-3p/FSCN1, miR-149-5p/IL-6, miR-1245b-5p/CASK, miR-628-5p/FOXP2, miR-326/Hnrnpa2b1, miR-195-5p/FKBP1A, miR-15b/IGF1R, miR-494-3p/STAT3, miR-486-5p/GOLPH3, miR-15a-5p/KIF23 and miR-101/Rap1A are among putative miRNA/mRNA axes that are modulated by oncogenic lncRNAs in the context of prostate cancer.

Although expression profile of lncRNAs have been comprhensively assessed in tumoral tissues of patients with prostate cancer, less effort has been made for analysis of their expression in urine or serum samples. Based on the availability of these sources for non-invasive diagnostic procedures, future studies should focus on these biofluids to facilitate early detection of prostate cancer via non-invasive methods.

Taken together, lncRNAs have been found to contribute to the pathogenesis of prostate cancer through various mechanisms. These transcripts can be used as targets for therapeutic interventions in this kind of cancer.

 Author contributions

MT and AB designed and supervised the study. SG-F wrote the draft and revised it. EB, BH, and AK collected the data and designed the figures and tables. All authors contributed to the article and approved the submitted version.

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

 References Siegel RL Miller KD Fuchs HE Jemal A . Cancer statistic. CA Cancer J Clin (2022) 72:7–33. doi: 10.3322/caac.21708 Gann PH . Risk factors for prostate cancer. Rev Urol (2002) 4 Suppl 5:S3–S10. Huncharek M Haddock KS Reid R Kupelnick B . Smoking as a risk factor for prostate cancer: A meta-analysis of 24 prospective cohort studies. Am J Public Health (2010) 100:693–701. doi: 10.2105/AJPH.2008.150508 Wang G Zhao D Spring DJ Depinho RA . Genetics and biology of prostate cancer. Genes Dev (2018) 32:1105–40. doi: 10.1101/gad.315739.118 Epstein JI Egevad L Amin MB Delahunt B Srigley JR Humphrey PA . The 2014 international society of urological pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol (2016) 40:244–52. doi: 10.1097/PAS.0000000000000530 Huggins C Hodges CV . Studies on prostatic cancer. Cancer Res (1941) 1:293–7. doi: 10.1001/archsurg.1941.01210140043004 Misawa A Takayama KI Inoue S . Long non-coding RNAs and prostate cancer. Cancer Sci (2017) 108:2107–14. doi: 10.1111/cas.13352 Taheri M Pouresmaeili F Omrani MD Habibi M Sarrafzadeh S Noroozi R . Association of ANRIL gene polymorphisms with prostate cancer and benign prostatic hyperplasia in an Iranian population. Biomarkers Med (2017) 11:413–22. doi: 10.2217/bmm-2016-0378 Taheri M Khoshbakht T Jamali E Kallenbach J Ghafouri-Fard S Baniahmad A . Interaction between non-coding RNAs and androgen receptor with an especial focus on prostate cancer. Cells (2021) 10. doi: 10.3390/cells10113198 Ghafouri-Fard S Dashti S Hussen BM Farsi M Taheri M . BCYRN1: An oncogenic lncRNA in diverse cancers. Pathol - Res Pract (2021) 220:153385. doi: 10.1016/j.prp.2021.153385 Prensner JR Chinnaiyan AM . The emergence of lncRNAs in cancer biology. Cancer Discov (2011) 1:391–407. doi: 10.1158/2159-8290.CD-11-0209 Hussen BM Azimi T Abak A Hidayat HJ Taheri M Ghafouri-Fard S . Role of lncRNA BANCR in human cancers: An updated review. Front Cell Dev Biol (2021) 9. doi: 10.3389/fcell.2021.689992 Xia KG Wang CM Shen DY Song XY Mu XY Zhou JW . LncRNA NEAT1-associated aerobic glycolysis blunts tumor immunosurveillance by T cells in prostate cancer. Neoplasma (2022) 69:594–602. doi: 10.4149/neo_2022_211021N1497 Sun X Xin S Zhang Y Jin L Liu X Zhang J . Long non−coding RNA CASC11 interacts with YBX1 to promote prostate cancer progression by suppressing the p53 pathway. Int J Oncol (2022) 61. Capik O Sanli F Kurt A Ceylan O Suer I Kaya M . CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis. Prostate Cancer Prostatic Dis (2021) 24:891–902. doi: 10.1038/s41391-021-00353-0 Zhao H Dong H Wang P Zhu H . Long non-coding RNA SNHG17 enhances the aggressiveness of C4-2 human prostate cancer cells in association with β-catenin signaling. Oncol Lett (2021) 21:472. doi: 10.3892/ol.2021.12733 Wu G Hao C Qi X Nie J Zhou W Huang J . LncRNA SNHG17 aggravated prostate cancer progression through regulating its homolog SNORA71B via a positive feedback loop. Cell Death Dis (2020) 11:393. doi: 10.1038/s41419-020-2569-y Bai M Lei Y Wang M Ma J Yang P Mou X . Long non-coding RNA SNHG17 promotes cell proliferation and invasion in castration-resistant prostate cancer by targeting the miR-144/CD51 axis. Front Genet (2020) 11:274. doi: 10.3389/fgene.2020.00274 Weng W Liu C Li G Ruan Q Li H Lin N . Long non-−coding RNA SNHG16 functions as a tumor activator by sponging miR−373−3p to regulate the TGF−β−R2/SMAD pathway in prostate cancer. Mol Med Rep (2021) 24. Shao M Yu Z Zou J . LncRNA-SNHG16 silencing inhibits prostate carcinoma cell growth, downregulate GLUT1 expression and reduce glucose uptake. Cancer Manag Res (2020) 12:1751–7. doi: 10.2147/CMAR.S231370 Luo ZF Peng Y Liu FH Ma JS Hu G Lai SL . Long noncoding RNA SNHG14 promotes malignancy of prostate cancer by regulating with miR-5590-3p/YY1 axis. Eur Rev Med Pharmacol Sci (2020) 24:4697–709. Chen Z Qi T Qin XP Wang J Huang ZS Hu XY . Long noncoding RNA SNHG12 promotes prostate tumor occurrence and progression via AKT regulation. BioMed Res Int (2020) 2020:8812923. doi: 10.1155/2020/8812923 Wang X He C Yang Z Li S Qiao L Fang L . Dysregulation of long non-coding RNA SNHG12 alters the viability, apoptosis, and autophagy of prostate cancer cells by regulating miR-195/CCNE1 axis. Int J Clin Exp Pathol (2019) 12:1272–83. Li Y Pan B Guo X Meng X Tian X . Prognostic value of long noncoding RNA SNHG11 in patients with prostate cancer. Horm Metab Res (2022) 54:187–93. doi: 10.1055/a-1745-8952 Xie Q Zhao S Kang R Wang X . lncRNA SNHG11 facilitates prostate cancer progression through the upregulation of IGF−1R expression and by sponging miR−184. Int J Mol Med (2021) 48. Chen Q Yang X Gong B Xie W Ma M Fu S . SNHG10 is a prognostic biomarker correlated with immune infiltrates in prostate cancer. Front Cell Dev Biol (2021) 9:731042. doi: 10.3389/fcell.2021.731042 Li C Hu J Hu X Zhao C Mo M Zu X . LncRNA SNHG9 is a prognostic biomarker and correlated with immune infiltrates in prostate cancer. Transl Androl Urol (2021) 10:215–26. doi: 10.21037/tau-20-1134 Shi Z Zhang H Jie S Yang X Huang Q Mao Y . Long non-coding RNA SNHG8 promotes prostate cancer progression through repressing miR-384 and up-regulating HOXB7. J Gene Med (2021) 23:e3309. doi: 10.1002/jgm.3309 Liu J Yuan JF Wang YZ . METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in prostate cancer via SRSF1/c-myc axis. Exp Cell Res (2022) 416:113149. doi: 10.1016/j.yexcr.2022.113149 Xia Q Li J Yang Z Zhang D Tian J Gu B . Long non-coding RNA small nucleolar RNA host gene 7 expression level in prostate cancer tissues predicts the prognosis of patients with prostate cancer. Med (Baltimore) (2020) 99:e18993. doi: 10.1097/MD.0000000000018993 Cao C Sun G Liu C . Long non-coding RNA SNHG6 regulates the sensitivity of prostate cancer cells to paclitaxel by sponging miR-186. Cancer Cell Int (2020) 20:381. doi: 10.1186/s12935-020-01462-x Xi X Hu Z Wu Q Hu K Cao Z Zhou J . High expression of small nucleolar RNA host gene 3 predicts poor prognosis and promotes bone metastasis in prostate cancer by activating transforming growth factor-beta signaling. Bioengineered (2022) 13:1895–907. doi: 10.1080/21655979.2021.2020393 Wang X Song Y Shi Y Yang D Li J Yin B . SNHG3 could promote prostate cancer progression through reducing methionine dependence of PCa cells. Cell Mol Biol Lett (2022) 27:13. doi: 10.1186/s11658-022-00313-z Yu L Ren Y . Long noncoding RNA small nucleolar RNA host gene 3 mediates prostate cancer migration, invasion, and epithelial-mesenchymal transition by sponging miR-487a-3p to regulate TRIM25. Cancer Biother Radiopharm (2022) 37:451–65. doi: 10.1089/cbr.2020.3988 Li T Xing Y Yang F Sun Y Zhang S Wang Q . LncRNA SNHG3 sponges miR-577 to up-regulate SMURF1 expression in prostate cancer. Cancer Med (2020) 9:3862–52. doi: 10.1002/cam4.2992 Tan X Chen WB Lv DJ Yang TW Wu KH Zou LB . LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer. Cell Death Dis (2021) 12:138. doi: 10.1038/s41419-021-03413-4 Xiong H Shen J Chen Z Yang J Xie B Jia Y . H19/let−7/Lin28 ceRNA network mediates autophagy inhibiting epithelial−mesenchymal transition in breast cancer. Int J Oncol (2020) 56:794–806. Tang Q Li Z Han W Cheng S Wang Y . High expression of lncRNA SNHG1 in prostate cancer patients and inhibition of SNHG1 suppresses cell proliferation and promotes apoptosis. Indian J Pathol Microbiol (2020) 63:575–80. doi: 10.4103/IJPM.IJPM_612_19 Meng XF Liu AD Li SL . SNHG1 promotes proliferation, invasion and EMT of prostate cancer cells through miR-195-5p. Eur Rev Med Pharmacol Sci (2020) 24:9880–8. Xie M Zhang Z Cui Y . Long noncoding RNA SNHG1 contributes to the promotion of prostate cancer cells through regulating miR-377-3p/AKT2 axis. Cancer Biother Radiopharm (2020) 35:109–19. doi: 10.1089/cbr.2019.3177 Ge Y Liu L Luo L Fang Y Ni T . MIR22HG aggravates oxygen-glucose deprivation and reoxygenation-induced cardiomyocyte injury through the miR-9-3p/SH2B3 axis. Cardiovasc Ther (2022) 2022:7332298. doi: 10.1155/2022/7332298 Liang D Tian C Zhang X . lncRNA MNX1−AS1 promotes prostate cancer progression through regulating miR−2113/MDM2 axis. Mol Med Rep (2022) 26. Huang F Zhou LQ . Effect and mechanism of lncRNA CERS6-AS1 on the biological behavior of prostate cancer cell. Appl Bionics Biomech (2022) 2022:9292538. doi: 10.1155/2022/9292538 Wang YY Chen C . lncRNA-DANCR promotes taxol resistance of prostate cancer cells through modulating the miR-33b-5p-LDHA axis. Dis Markers (2022) 2022:9516774. doi: 10.1155/2022/9516774 Deng H Zhu B Dong Z Jiang H Zhao X Wu S . miR-214-5p targeted by LncRNA DANCR mediates TGF-β signaling pathway to accelerate proliferation, migration and inhibit apoptosis of prostate cancer cells. Am J Transl Res (2021) 13:2224–40. Sun W Zu S Shao G Wang W Gong F . Long non-coding DANCR targets miR-185-5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3β/snail pathway. J Gene Med (2021) 23:e3344. doi: 10.1002/jgm.3344 Mu X Shen Z Lin Y Xiao J Xia K Xu C . LncRNA-MALAT1 regulates cancer glucose metabolism in prostate cancer via MYBL2/mTOR axis. Oxid Med Cell Longev (2022) 2022:8693259. doi: 10.1155/2022/8693259 Hao T Wang Z Yang J Zhang Y Shang Y Sun J . MALAT1 knockdown inhibits prostate cancer progression by regulating miR-140/BIRC6 axis. BioMed Pharmacother (2020) 123:109666. doi: 10.1016/j.biopha.2019.109666 Ferri C Di Biase A Bocchetti M Zappavigna S Wagner S Le Vu P . MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. J Exp Clin Cancer Res (2022) 41:20. doi: 10.1186/s13046-021-02233-w Zhang D Fang C Li H Lu C Huang J Pan J . Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145. Transl Androl Urol (2021) 10:2307–19. doi: 10.21037/tau-20-1526 Li Y Ji J Lyu J Jin X He X Mo S . A novel urine exosomal lncRNA assay to improve the detection of prostate cancer at initial biopsy: A retrospective multicenter diagnostic feasibility study. Cancers (Basel) (2021) 13. doi: 10.3390/cancers13164075 Liu H He X Li T Qu Y Xu L Hou Y . PCGEM1 promotes proliferation, migration and invasion in prostate cancer by sponging miR-506 to upregulate TRIAP1. BMC Urol (2022) 22:14. doi: 10.1186/s12894-022-00969-x Bai J Huang G . Role of long non-coding RNA NEAT1 in the prognosis of prostate cancer patients. Med (Baltimore) (2020) 99:e20204. doi: 10.1097/MD.0000000000020204 Zhao W Zhu X Jin Q Lin B Ji R . The lncRNA NEAT1/miRNA-766-5p/E2F3 regulatory axis promotes prostate cancer progression. J Oncol (2022) 2022:1866972. doi: 10.1155/2022/1866972 Nitusca D Marcu A Dema A Balacescu L Balacescu O Bardan R . Long noncoding RNA NEAT1 as a potential candidate biomarker for prostate cancer. Life (Basel) (2021) 11. doi: 10.3390/life11040320 Wen S Wei Y Zen C Xiong W Niu Y Zhao Y . Long non-coding RNA NEAT1 promotes bone metastasis of prostate cancer through N6-methyladenosine. Mol Cancer (2020) 19:171. doi: 10.1186/s12943-020-01293-4 Zhou J Li J Qian C Qiu F Shen Q Tong R . LINC00624/TEX10/NF-κB axis promotes proliferation and migration of human prostate cancer cells. Biochem Biophys Res Commun (2022) 601:1–8. doi: 10.1016/j.bbrc.2022.02.078 Arslan A Batar B Temiz E Tozkir H Koyuncu I Bozgeyik E . Silencing of TP73-AS1 impairs prostate cancer cell proliferation and induces apoptosis via regulation of TP73. Mol Biol Rep (2022) 49:6859–69. doi: 10.1007/s11033-022-07141-6 Qin D Ni C Tan B Huang S Deng B Huang Z . LINC01207 promotes prostate cancer progression by sponging miR-1182 to upregulate AKT3. Oncol Lett (2022) 23:57. doi: 10.3892/ol.2021.13175 Yan Y Liu J Xu Z Ye M Li J . lncRNA PCAT14 is a diagnostic marker for prostate cancer and is associated with immune cell infiltration. Dis Markers (2021) 2021:9494619. doi: 10.1155/2021/9494619 Li P Xu H Yang L Zhan M Shi Y Zhang C . E2F transcription factor 2-activated DLEU2 contributes to prostate tumorigenesis by upregulating serum and glucocorticoid-induced protein kinase 1. Cell Death Dis (2022) 13:77. doi: 10.1038/s41419-022-04525-1 Cai Z Wu Y Ju G Wang G Liu B . Role of BCAR4 in prostate cancer cell autophagy. Transl Androl Urol (2021) 10:4253–61. doi: 10.21037/tau-21-929 Ye C Qin S Guo F Yang Y Wang H Zhang C . LncRNA EIF3J-AS1 functions as an oncogene by regulating MAFG to promote prostate cancer progression. J Cancer (2022) 13:146–52. doi: 10.7150/jca.60676 Ahani M Ghaderian SMH Mehr Azma M Kamali K Naghavi Gargari B Bahramali G . Differential gene expression of BCL-2, ZEB2-AS1 and BALR-2 in prostate cancer and benign prostatic hyperplasia. Andrologia (2022) 54:e14344. doi: 10.1111/and.14344 Jiang Y Zhao H Chen Y Li K Li T Chen J . Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis. Cell Death Dis (2021) 12:1129. doi: 10.1038/s41419-021-04421-0 Cheng Y Xiong HY Li YM Zuo HR Liu Y Liao GL . LncRNA HOXA11-AS promotes cell growth by sponging miR-24-3p to regulate JPT1 in prostate cancer. Eur Rev Med Pharmacol Sci (2021) 25:4668–77. Yang C Shen S Zheng X Ye K Ge H Sun Y . Long non-coding RNA LINC00337 induces autophagy and chemoresistance to cisplatin in esophageal squamous cell carcinoma cells via upregulation of TPX2 by recruiting E2F4. FASEB J (2020) 34. doi: 10.1096/fj.201900731RR Pan X Chen G Hu W . lncRNA HLA complex group 18 (HCG18) facilitated cell proliferation, invasion, and migration of prostate cancer through modulating miR-370-3p/DDX3X axis. Reprod Sci (2021) 28:3406–16. doi: 10.1007/s43032-021-00614-2 Peng N Zhang Z Wang Y Yang M Fan J Wang Q . Down-regulated LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/FZD5/Wnt/β-catenin axis. J Cell Mol Med (2021) 25:10627–10637. doi: 10.1111/jcmm.17000 Qu W Wei X Zhang H Hou J . FOXD1-AS1 promotes malignant behaviours of prostate cancer cells via the miR-3167/YWHAZ axis. Andrologia (2022) 54:e14263. doi: 10.1111/and.14263 Fu C Xin J Zhang W Lai J Huang Z . LINC00992 exerts oncogenic activities in prostate cancer via regulation of SOX4. Exp Cell Res (2021) 408:112855. doi: 10.1016/j.yexcr.2021.112855 Cai X Dai Y Gao P Ren G Cheng D Wang B . LncRNA CCAT1 promotes prostate cancer cells proliferation, migration, and invasion through regulation of miR-490-3p/FRAT1 axis. Aging (Albany NY) (2021) 13:18527–44. doi: 10.18632/aging.203300 Li X Han X Wei P Yang J Sun J . Knockdown of lncRNA CCAT1 enhances sensitivity of paclitaxel in prostate cancer via regulating miR-24-3p and FSCN1. Cancer Biol Ther (2020) 21:452–62. doi: 10.1080/15384047.2020.1727700 Liu J Li Y Zhang Q Lv C Wang M Jiao Y . PVT1 expression is a predictor for poor survival of prostate cancer patients. Technol Cancer Res Treat (2021) 20:1533033820971610. doi: 10.1177/1533033820971610 Zhao X Liu Y Luo C Zuo Y . AGAP2-AS1/miR-628-5p/FOXP2 feedback loop facilitates the growth of prostate cancer via activating WNT pathway. Carcinogenesis (2021) 42:1270–80. doi: 10.1093/carcin/bgab062 Lang C Yin C Lin K Li Y Yang Q Wu Z . m(6) a modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization. Clin Transl Med (2021) 11:e426. doi: 10.1002/ctm2.426 Leng W Liu Q Zhang S Sun D Guo Y . LncRNA AFAP1-AS1 modulates the sensitivity of paclitaxel-resistant prostate cancer cells to paclitaxel via miR-195-5p/FKBP1A axis. Cancer Biol Ther (2020) 21:1072–80. doi: 10.1080/15384047.2020.1829266 Jiang H Deng W Zhu K Zeng Z Hu B Zhou Z . LINC00467 promotes prostate cancer progression via M2 macrophage polarization and the miR-494-3p/STAT3 axis. Front Oncol (2021) 11:661431. doi: 10.3389/fonc.2021.661431 Song HR Guo XB Duan Y Meng HY Wang ZY . PAX5-induced upregulation of LINC01194 exerts oncogenic properties by regulating GOLPH3 expression via miR-486-5p in prostate cancer. Eur Rev Med Pharmacol Sci (2021) 25:2528–41. Cui Z Gao H Yan N Dai Y Wang H Wang M . LncRNA PlncRNA-1 accelerates the progression of prostate cancer by regulating PTEN/Akt axis. Aging (Albany NY) (2021) 13:12113–28. doi: 10.18632/aging.202919 Xing P Wang Y Zhang L Ma C Lu J . Knockdown of lncRNA MIR4435−2HG and ST8SIA1 expression inhibits the proliferation, invasion and migration of prostate cancer cells in vitro and in vivo by blocking the activation of the FAK/AKT/β−catenin signaling pathway. Int J Mol Med (2021) 47. Sun F Wu K Yao Z Mu X Zheng Z Sun M . Long noncoding RNA PVT1 promotes prostate cancer metastasis by increasing NOP2 expression via targeting tumor suppressor MicroRNAs. Onco Targets Ther (2020) 13:6755–65. doi: 10.2147/OTT.S242441 Pan Z Wu C Li Y Li H An Y Wang G . LncRNA DANCR silence inhibits SOX5-medicated progression and autophagy in osteosarcoma via regulating miR-216a-5p. Biomed Pharmacother (2020) 122:109707. doi: 10.1016/j.biopha.2019.109707 Yu S Yu H Zhang Y Liu C Zhang W Zhang Y . Long non-coding RNA LINC01116 acts as an oncogene in prostate cancer cells through regulation of miR-744-5p/UBE2L3 axis. Cancer Cell Int (2021) 21:168. doi: 10.1186/s12935-021-01843-w Hasan MF Ganapathy K Sun J Khatib A Andl T Soulakova JN . LncRNA PAINT is associated with aggressive prostate cancer and dysregulation of cancer hallmark genes. Int J Cancer (2021) 149. doi: 10.1101/2020.10.29.361105 Zheng Z Qiu K Huang W . Long non-coding RNA (lncRNA) RAMS11 promotes metastatis and cell growth of prostate cancer by CBX4 complex binding to Top2α. Cancer Manag Res (2021) 13:913–23. doi: 10.2147/CMAR.S270144 Hu CY Chen J Qin XH You P Ma J Zhang J . Long non-coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer. J Exp Clin Cancer Res (2021) 40:98. doi: 10.1186/s13046-021-01891-0 Zhang Y Li Y . Long non-coding RNA NORAD contributes to the proliferation, invasion and EMT progression of prostate cancer via the miR-30a-5p/RAB11A/WNT/β-catenin pathway. Cancer Cell Int (2020) 20:571. doi: 10.1186/s12935-020-01665-2 Chen QH Li B Liu DG Zhang B Yang X Tu YL . LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1. Cancer Cell Int (2020) 20:394. doi: 10.1186/s12935-020-01481-8 Xie H Zhao J Wan J Zhao J Wang Q Yang X . Long non−coding RNA AC245100.4 promotes prostate cancer tumorigenesis via the microRNA−145−5p/RBBP5 axis. Oncol Rep (2021) 45:619–29. doi: 10.3892/or.2020.7894 Liao B Chen S Li Y Yang Z Yang Y Deng X . LncRNA BLACAT1 promotes proliferation, migration and invasion of prostate cancer cells via regulating miR-29a-3p/DVL3 axis. Technol Cancer Res Treat (2021) 20:1533033820972342. doi: 10.1177/1533033820972342 Xiu D Liu L Cheng M Sun X Ma X . Knockdown of lncRNA TUG1 enhances radiosensitivity of prostate cancer via the TUG1/miR-139-5p/SMC1A axis. Onco Targets Ther (2020) 13:2319–31. doi: 10.2147/OTT.S236860 Yao ZF Pan ZY Yao YW Chen JF . [Long noncoding RNA Linc00662 promotes the tumorigenesis of prostate cancer cells]. Zhonghua Nan Ke Xue (2020) 26:588–94. Wu J Lv Y Li Y Jiang Y Wang L Zhang X . MCM3AP-AS1/miR-876-5p/WNT5A axis regulates the proliferation of prostate cancer cells. Cancer Cell Int (2020) 20:307. doi: 10.1186/s12935-020-01365-x Dong W Liu X Yang C Wang D Xue Y Ruan X . Glioma glycolipid metabolism: MSI2-SNORD12B-FIP1L1-ZBTB4 feedback loop as a potential treatment target. Clin Transl Med (2021) 11:e411. doi: 10.1002/ctm2.411 Yi S Li G Sun B . Overexpression of LINC00852 promotes prostate cancer cell proliferation and metastasis. Asia Pac J Clin Oncol (2021) 17:435–41. doi: 10.1111/ajco.13418 Cui R Liu C Lin P Xie H Wang W Zhao J . LncRNA AC245100.4 binds HSP90 to promote the proliferation of prostate cancer. Epigenomics (2020) 12:1257–71. doi: 10.2217/epi-2020-0270 Zeng C Fan D Xu Y Li X Yuan J Yang Q . Curcumol enhances the sensitivity of doxorubicin in triple-negative breast cancer via regulating the miR-181b-2-3p-ABCC3 axis. Biochem Pharmacol (2020) 174:113795. doi: 10.1016/j.bcp.2020.113795 Zhu X Ma X Zhao S Cao Z . DLX6-AS1 accelerates cell proliferation through regulating miR-497-5p/SNCG pathway in prostate cancer. Environ Toxicol (2021) 36:308–19. doi: 10.1002/tox.23036 Wen Y Gong X Dong Y Tang C . Long non coding RNA SNHG16 facilitates proliferation, migration, invasion and autophagy of neuroblastoma cells via sponging miR-542-3p and upregulating ATG5 expression. OncoTargets Ther (2020) 13:263. doi: 10.2147/OTT.S226915 Yao C Cheng X Guo X Lu X Bu F Xu Y . NNT-AS1 modulates prostate cancer cell proliferation, apoptosis and migration through miR-496/DDIT4 axis. Cancer Cell Int (2020) 20:463. doi: 10.1186/s12935-020-01505-3 Leidal AM Huang HH Marsh T Solvik T Zhang D Ye J . The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles. Nat Cell Biol (2020) 22:187–99. doi: 10.1038/s41556-019-0450-y Wu S Ding L Xu H Gao J Shao Y Zhang S . The long non-coding RNA IDH1-AS1 promotes prostate cancer progression by enhancing IDH1 enzyme activity. Onco Targets Ther (2020) 13:7897–906. doi: 10.2147/OTT.S251915 Yao L Yang L Song H Liu T Yan H . Silencing of lncRNA XIST suppresses proliferation and autophagy and enhances vincristine sensitivity in retinoblastoma cells by sponging miR-204-5p. Eur Rev Med Pharmacol Sci (2020) 24:3526–37. Song X Wang H Wu J Sun Y . Long noncoding RNA SOX2-OT knockdown inhibits proliferation and metastasis of prostate cancer cells through modulating the miR-452-5p/HMGB3 axis and inactivating wnt/β-catenin pathway. Cancer Biother Radiopharm (2020) 35:682–95. doi: 10.1089/cbr.2019.3479 Angeles AK Heckmann D Flosdorf N Duensing S Sültmann H . The ERG-regulated LINC00920 promotes prostate cancer cell survival via the 14-3-3ϵ-FOXO pathway. Mol Cancer Res (2020) 18:1545–59. doi: 10.1158/1541-7786.MCR-20-0021 Meng L Li Z Chen Y Liu D Liu Z . LINC00689 promotes prostate cancer progression via regulating miR-496/CTNNB1 to activate wnt pathway. Cancer Cell Int (2020) 20:215. doi: 10.1186/s12935-020-01280-1 Xing Z Li S Liu Z Zhang C Meng M Bai Z . The long non-coding RNA LINC00473 contributes to cell proliferation via JAK-STAT3 signaling pathway by regulating miR-195-5p/SEPT2 axis in prostate cancer. Biosci Rep (2020) 40. doi: 10.1042/BSR20191850 Xie Y Gu J Qin Z Ren Z Wang Y Shi H . Long non-coding RNA FAM66C is associated with clinical progression and promotes cell proliferation by inhibiting proteasome pathway in prostate cancer. Cell Biochem Funct (2020) 38:1006–16. doi: 10.1002/cbf.3531 Ma T Chen H Wang P Yang N Bao J . Downregulation of lncRNA ZEB1-AS1 represses cell proliferation, migration, and invasion through mediating PI3K/AKT/mTOR signaling by miR-342-3p/CUL4B axis in prostate cancer. Cancer Biother Radiopharm (2020) 35:661–72. doi: 10.1089/cbr.2019.3123 Li G Yang J Chong T Huang Y Liu Y Li H . TUG1 knockdown inhibits the tumorigenesis and progression of prostate cancer by regulating microRNA-496/Wnt/β-catenin pathway. Anticancer Drugs (2020) 31:592–600. doi: 10.1097/CAD.0000000000000882 Hao SD Ma JX Liu Y Liu PJ Qin Y . Long non-coding TUG1 accelerates prostate cancer progression through regulating miR-128-3p/YES1 axis. Eur Rev Med Pharmacol Sci (2020) 24:619–32. Chen W Yu Z Huang W Yang Y Wang F Huang H . LncRNA LINC00665 promotes prostate cancer progression via miR-1224-5p/SND1 axis. Onco Targets Ther (2020) 13:2527–35. doi: 10.2147/OTT.S241578 Tan SF Ni JX Xiong H . LncRNA UNC5B-AS1 promotes malignant progression of prostate cancer by competitive binding to caspase-9. Eur Rev Med Pharmacol Sci (2020) 24:2271–80. Pan J Xu X Wang G . lncRNA ZFAS1 is involved in the proliferation, invasion and metastasis of prostate cancer cells through competitively binding to miR-135a-5p. Cancer Manag Res (2020) 12:1135–49. doi: 10.2147/CMAR.S237439 Fan L Li H Wang W . Long non-coding RNA PRRT3-AS1 silencing inhibits prostate cancer cell proliferation and promotes apoptosis and autophagy. Exp Physiol (2020) 105:793–808. doi: 10.1113/EP088011 Jiang Z Zhang Y Chen X Wu P Chen D . Long non-coding RNA LINC00673 silencing inhibits proliferation and drug resistance of prostate cancer cells via decreasing KLF4 promoter methylation. J Cell Mol Med (2020) 24:1878–92. doi: 10.1111/jcmm.14883 Guan Z Song Y Ma J Li F Zhao X Liang G . Altered expression of lncRNA NCK1-AS1 distinguished patients with prostate cancer from those with benign prostatic hyperplasia. Oncol Lett (2019) 18:6379–84. doi: 10.3892/ol.2019.11039 Zhang Y Zhang J Liang S Lang G Liu G Liu P . Long non-coding RNA VIM-AS1 promotes prostate cancer growth and invasion by regulating epithelial-mesenchymal transition. J buon (2019) 24:2090–8. Mao Y Li W Weng Y Hua B Gu X Lu C . METTL3-mediated m(6)A modification of lncRNA MALAT1 facilitates prostate cancer growth by activation of PI3K/AKT signaling. Cell Transplant (2022) 31:9636897221122997. doi: 10.1177/09636897221122997 Lu TT Tao X Li HL Gai L Huang H Li F . LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer. Asian J Androl (2022) 24. doi: 10.21203/rs.3.rs-218133/v1 Zeng Q Liu J Wu Q Song R Miao W Ma Y . Long non-coding RNA AC008972.1 as a novel therapeutic target for prostate cancer. Cancer Biother Radiopharm. (2022). doi: 10.1089/cbr.2022.0031 Takayama K Horie-Inoue K Katayama S Suzuki T Tsutsumi S Ikeda K . Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. EMBO J (2013) 32:1665–80. doi: 10.1038/emboj.2013.99 Zhang Y Pitchiaya S Cieślik M Niknafs YS Tien JC Hosono Y . Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression. Nat Genet (2018) 50:814–24. doi: 10.1038/s41588-018-0120-1 Takayama KI Fujimura T Suzuki Y Inoue S . Identification of long non-coding RNAs in advanced prostate cancer associated with androgen receptor splicing factors. Commun Biol (2020) 3:393. doi: 10.1038/s42003-020-01120-y Prensner JR Iyer MK Sahu A Asangani IA Cao Q Patel L . The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet (2013) 45:1392–8. doi: 10.1038/ng.2771 Prensner JR Chen W Han S Iyer MK Cao Q Kothari V . The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc. Neoplasia (2014) 16:900–8. doi: 10.1016/j.neo.2014.09.001 Zhang A Zhao JC Kim J Fong KW Yang YA Chakravarti D . LncRNA HOTAIR enhances the androgen-Receptor-Mediated transcriptional program and drives castration-resistant prostate cancer. Cell Rep (2015) 13:209–21. doi: 10.1016/j.celrep.2015.08.069 Chakravarty D Sboner A Nair SS Giannopoulou E Li R Hennig S . The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun (2014) 5:5383. doi: 10.1038/ncomms6383 Yang L Lin C Jin C Yang JC Tanasa B Li W . lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature (2013) 500:598–602. doi: 10.1038/nature12451 Misawa A Takayama K Urano T Inoue S . Androgen-induced long noncoding RNA (lncRNA) SOCS2-AS1 promotes cell growth and inhibits apoptosis in prostate cancer cells. J Biol Chem (2016) 291:17861–80. doi: 10.1074/jbc.M116.718536 Yu C Fan Y Zhang Y Liu L Guo G . LINC00893 inhibits the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway. Cancer Cell Int (2022) 22:228. doi: 10.1186/s12935-022-02637-4 Mi YY Sun CY Zhang LF Wang J Shao HB Qin F . Long non-coding RNAs LINC01679 as a competitive endogenous RNAs inhibits the development and progression of prostate cancer via regulating the miR-3150a-3p/SLC17A9 axis. Front Cell Dev Biol (2021) 9:737812. doi: 10.3389/fcell.2021.737812 Zhang W Shi C Xu Q Chen X Zhu H Zheng B . Long non-coding RNA MIR22HG suppresses cell proliferation and promotes apoptosis in prostate cancer cells by sponging microRNA-9-3p. Bioengineered (2022) 13:13108–17. doi: 10.1080/21655979.2022.2079244 Zhong B Zhao Z Jiang X . RP1-59D14.5 triggers autophagy and represses tumorigenesis and progression of prostate cancer via activation of the hippo signaling pathway. Cell Death Dis (2022) 13:458. doi: 10.1038/s41419-022-04865-y Wei X Hou Y Zhang Y Zhang H Sun Z Meng X . Long non-coding RNA MAGI2-AS3 inactivates STAT3 pathway to inhibit prostate cancer cell proliferation via acting as a microRNA-424-5p sponge. J Cancer (2022) 13:343–53. doi: 10.7150/jca.60749 Ghildiyal R Sawant M Renganathan A Mahajan K Kim EH Luo J . Loss of long noncoding RNA NXTAR in prostate cancer augments androgen receptor expression and enzalutamide resistance. Cancer Res (2022) 82:155–68. doi: 10.1158/0008-5472.CAN-20-3845 Li R Chen Y Wu J Cui X Zheng S Yan H . LncRNA FGF14-AS2 represses growth of prostate carcinoma cells via modulating miR-96-5p/AJAP1 axis. J Clin Lab Anal (2021) 35:e24012. doi: 10.1002/jcla.24012 Zhou Z Wu X Zhou Y Yan W . Long non-coding RNA ADAMTS9-AS1 inhibits the progression of prostate cancer by modulating the miR-142-5p/CCND1 axis. J Gene Med (2021) 23:e3331. doi: 10.1002/jgm.3331 Ding X Xu X He XF Yuan Y Chen C Shen XY . Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling. Bioengineered (2021) 12:803–14. doi: 10.1080/21655979.2021.1890383 Liu WH Lu JJ Yu RK Zhou L Yu Q Li DF . LINC00641 regulates prostate cancer cell growth and apoptosis via the miR-365a-3p/VGLL4 axis. Eur Rev Med Pharmacol Sci (2021) 25:108–15. Du L Gao Y . PGM5-AS1 impairs miR-587-mediated GDF10 inhibition and abrogates progression of prostate cancer. J Transl Med (2021) 19:12. doi: 10.1186/s12967-020-02572-w Ma X Wang Z Ren H Bao X Zhang Y Wang B . Long non-coding RNA GAS5 suppresses tumor progression and enhances the radiosensitivity of prostate cancer through the miR-320a/RAB21 axis. Cancer Manag Res (2020) 12:8833–45. doi: 10.2147/CMAR.S244123 Li Y Li H Wei X . Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3. Cancer Cell Int (2020) 20:474. doi: 10.1186/s12935-020-01484-5 Huo W Qi F Wang K . Long non-coding RNA FER1L4 inhibits prostate cancer progression via sponging miR-92a-3p and upregulation of FBXW7. Cancer Cell Int (2020) 20:64. doi: 10.1186/s12935-020-1143-0 Qiu K Zheng Z Huang Y . Long intergenic noncoding RNA 00844 promotes apoptosis and represses proliferation of prostate cancer cells through upregulating GSTP1 by recruiting EBF1. J Cell Physiol (2020) 235:8472–85. doi: 10.1002/jcp.29690 Zhou J Song Q Liu X Ye H Wang Y Zhang L . lncRNA Erbb4-IR is downregulated in prostate carcinoma and predicts prognosis. Oncol Lett (2020) 19:3425–30. doi: 10.3892/ol.2020.11464 Shen H Weng XD Yang D Wang L Liu XH . Long noncoding RNA MIR22HG is down-regulated in prostate cancer. Math Biosci Eng (2019) 17:1776–86. doi: 10.3934/mbe.2020093 Fan L Li H Zhang Y . LINC00908 negatively regulates microRNA-483-5p to increase TSPYL5 expression and inhibit the development of prostate cancer. Cancer Cell Int (2020) 20:10. doi: 10.1186/s12935-019-1073-x Li B Guo Z Liang Q Zhou H Luo Y He S . lncRNA DGCR5 up-regulates TGF-β1, increases cancer cell stemness and predicts survival of prostate cancer patients. Cancer Manag Res (2019) 11:10657–63. doi: 10.2147/CMAR.S231112 Ghafouri-Fard S Khoshbakht T Hussen BM Baniahmad A Taheri M Rashnoo F . A review on the role of PCA3 lncRNA in carcinogenesis with an especial focus on prostate cancer. Pathol-Res Pract (2022) 231:153800. doi: 10.1016/j.prp.2022.153800 Lin CY Wang SS Yang CK Li JR Chen CS Hung SC . Impact of GAS5 genetic polymorphism on prostate cancer susceptibility and clinicopathologic characteristics. Int J Med Sci (2019) 16:1424–9. doi: 10.7150/ijms.38080 Zhao L Zheng W Li C . Association of long-chain non-coding RNA GAS5 gene polymorphisms with prostate cancer risk and prognosis in Chinese han population. Med (Baltimore) (2020) 99:e21790. doi: 10.1097/MD.0000000000021790 Huang S Cui H Lou Z Wang X Chen L Xie Z . Association of rs3787016 in long non-coding RNAs POLR2E and rs2910164 in MiRNA-146a with prostate cancer: A systematic review and meta-analysis. Iran J Public Health (2018) 47:623–32. Xu B Zhang M Liu C Wang C You Z Wang Y . Association of long non-coding RNA MEG3 polymorphisms and risk of prostate cancer in Chinese han population. Urol J (2020) 18:176–80. Hu JC Wang SS Chou YE Chiu KY Li JR Chen CS . Associations between LncRNA MALAT1 polymorphisms and lymph node metastasis in prostate cancer. Diagn (Basel) (2021) 11. doi: 10.3390/diagnostics11091692 Taheri M Habibi M Noroozi R Rakhshan A Sarrafzadeh S Sayad A . HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population. Gene (2017) 613:20–4. doi: 10.1016/j.gene.2017.02.031 Groskopf J Aubin SM Deras IL Blase A Bodrug S Clark C . APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem (2006) 52:1089–95. doi: 10.1373/clinchem.2005.063289 Fotouhi Ghiam A Taeb S Huang X Huang V Ray J Scarcello S . Long non-coding RNA urothelial carcinoma associated 1 (UCA1) mediates radiation response in prostate cancer. Oncotarget (2017) 8:4668–89. doi: 10.18632/oncotarget.13576 Mirzaei S Paskeh MDA Okina E Gholami MH Hushmandi K Hashemi M . Molecular landscape of LncRNAs in prostate cancer: A focus on pathways and therapeutic targets for intervention. J Exp Clin Cancer Res (2022) 41:214. doi: 10.1186/s13046-022-02406-1 Pucci P Venalainen E Alborelli I Quagliata L Hawkes C Mather R . LncRNA HORAS5 promotes taxane resistance in castration-resistant prostate cancer via a BCL2A1-dependent mechanism. Epigenomics (2020) 12:1123–38. doi: 10.2217/epi-2019-0316