Front. Genet. Frontiers in Genetics Front. Genet. 1664-8021 Frontiers Media S.A. 1116445 10.3389/fgene.2023.1116445 Genetics Review A review on the role of LINC00511 in cancer Ghafouri-Fard et al. 10.3389/fgene.2023.1116445 Ghafouri-Fard Soudeh 1 Safarzadeh Arash 2 Hussen Bashdar Mahmud 3 Taheri Mohammad 4 5 * Ayatollahi Seyed Abdulmajid 6 * 1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Erbil, Iraq 4 Institute of Human Genetics, Jena University Hospital, Jena, Germany 5 Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 6 Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Edited by: Yujing Li, Emory University, United States

Reviewed by: Yulin Jin, Emory University, United States

Yangping Li, Emory University, United States

 *Correspondence: Mohammad Taheri, mohammad.taheri@uni-jena.de; Seyed Abdulmajid Ayatollahi, majid_ayatollahi@yahoo.com 14 04 2023 2023 14 1116445 05 12 2022 05 04 2023 Copyright © 2023 Ghafouri-Fard, Safarzadeh, Hussen, Taheri and Ayatollahi. 2023 Ghafouri-Fard, Safarzadeh, Hussen, Taheri and Ayatollahi

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Long Intergenic Non-Protein Coding RNA 511 (LINC00511) is an RNA gene being mostly associated with lung cancer. Further assessments have shown dysregulation of this lncRNA in a variety of cancers. LINC00511 has interactions with hsa-miR-29b-3p, hsa-miR-765, hsa-mir-150, miR-1231, TFAP2A-AS2, hsa-miR-185-3p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, RAD51-AS1 and EZH2. A number of transcription factors have been identified that regulate expression of LINC00511. The current narrative review summarizes the role of LINC00511 in different cancers with an especial focus on its prognostic impact in human cancers.

 LINC00511 cancer biomarker expression diagnostic section-at-acceptance RNA Introduction

Long non-coding RNAs (lncRNAs) are widely expressed transcripts with essential roles in gene regulation. Based on the results of the Human GENCODE project, the number of lncRNA genes in the human genome is estimated to surpass 16,000 (Fang et al., 2018). These transcripts embrace lncRNAs transcribed by RNA polymerase II, gene-overlapping antisense transcripts as well as lncRNAs from intergenic regions (lincRNAs) (Ghafouri-Fard et al., 2020; Ghafouri-Fard et al., 2021; Statello et al., 2021). Typically, lncRNAs have a 7-methyl guanosine cap at the 5′end and a polyadenylated tail at the 3′ends. Moreover, lncRNAs are spliced in a similar manner to mRNAs (Statello et al., 2021). However, several RNA polymerase II-transcribed lncRNAs are incompetently processed and are held in the nuclear compartment (Statello et al., 2021). LncRNAs interact with DNA, RNA and proteins. Through these interactions, lncRNAs influence chromatin structure and function, affect the assembly of nuclear bodies, change the stability and expression of mRNAs within the cytoplasm and regulate signaling pathways (Statello et al., 2021; Hussen et al., 2022). In comparison with mRNA promoters, lincRNA promoters have been found to be devoid of transcription factor binding sites, but having binding sites for a number of specific factors such as GATA and FOS (Melé et al., 2017).

Long Intergenic Non-Protein Coding RNA 511 (LINC00511) is an RNA gene being mostly associated with lung cancer. This lncRNA is encoded on chr17:72,290,091-72,640,472 (GRCh38/hg38), minus strand. Notably, more than 100 alternatively splice variants have been recognized for LINC00511. Except for two variants with retained introns (LINC00511-279 with 3766 bp and LINC00511-278 with 508 bp), other are affiliated with lncRNA group of transcripts (https://asia.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000227036; r=17:72290091-72640472). This lncRNA has important roles in the development of cancers and can be used as a possible diagnostic and prognostic marker in cancer. Abnormal expression of LINC00511 in a wide array of malignancies potentiates it as a target for therapeutic interventions. Based on DIANA-LncBase database (https://diana.e-ce.uth.gr/lncbasev3) (Karagkouni et al., 2020), expression of LINC00511 in various tissues and cell types have been investigated. With medium and high TPM levels and in homosapiens, the highest level of expression of LINC00511 is in prostate tissue and PC3 cell type along with cancer/malignant category.

The current narrative review summarizes the role of LINC00511 in different cancers with an especial focus on its prognostic impact in human cancers.

LINC00511 in cancers

Several studies have reported dysregulation (mainly upregulation) of LINC00511 in different cancers. These studies have also identified miRNAs that are sponged by LINC00511.

 Breast cancer

In breast cancer, LINC00511 has been found to be highly expressed in the clinical samples and its over-expression has been correlated with poor prognosis (Lu et al., 2018). Functional studies have shown that LINC00511 promotes proliferation, sphere-formation capacity, expression of stem factors and growth of breast tumors (Lu et al., 2018). From a mechanical point of view, LINC00511 acts as a molecular sponge for miR-185-3p to enhance expression of E2F1 protein. Besides, E2F1 binds with the promoter of Nanog gene and increases its expression (Figure 1). Therefore, LINC00511/miR-185-3p/E2F1/Nanog axis has been identified as an important route for induction of stemness and tumorigenesis in breast cancer (Lu et al., 2018). Another study in breast cancer has revealed more than 180 potential targets for LINC00511 through siRNA and RNA-seq assays. Bioinformatics analyses have shown relation between differently expressed genes and signaling pathways mediated by p38-α and p38-β. LINC00511 has been found to be mainly located in the cytoplasm regulating expression of MMP13 through sponging miR-150 (Shi et al., 2021). Expression of LINC00511 in breast cancer samples has been closely correlated with the presence of lymph node metastasis, greater tumor size and molecular subtypes of breast cancer. This lncRNA has been found to increase migratory potential and invasive ability of MDA-MB-231 and MCF-7 cells. Moreover, expression of LINC00511 has been shown to be increased by DNA hypomethylation. In turn, LINC00511 could promote expressions of Wnt10A, E2F2, TGFA, and MET and reduce sensitivity of breast cancer cells to Panobinostat (Liu et al., 2021a). LINC00511 can also influence the cytotoxic effects of paclitaxel on breast cancer cells through regulating miR-29c/CDK6 axis (Zhu et al., 2019).

A graphical illustration of the oncogenic role that LINC00511 performs in the environment of the many types of cancer.

Another study in patients with breast cancer has reported upregulation of LINC00511 and miR-301a-3p in patients’ blood parallel with downregulation of miR-185-3p (Mahmoud et al., 2021). Notably, LINC00511 expression has been increased in early stages of breast cancer. Area under the reciever operating characteristic curves of LINC00511, miR-185-3p, and miR-301a-3p has been superior to classical tumor markers indicating the diagnostic values of these transcripts as molecular biomarkers in liquid biopsy. Moreover, expression of LINC00511 has been correlated with lymph node metastasis and advanced tumor grades (Mahmoud et al., 2021). Additionally, the sponging effect of LINC00511 on miR-185 has been shown to be involved in breast cancer recurrence and radioresistance via regulation of STXBP4 expression (Liu et al., 2019). In breast cancer cells, LINC00511 expression induced by TFAP-2 expression and directly affected by ER deficiency at the transcriptional level. Through its interaction with EZH2, LINC00511 has been shown to encourage tumor development and suppress apoptosis (Figure 2) (Zhang et al., 2019). Table 1 summarizes the results of studies regarding the role of this lncRNA in breast cancer.

The carcinogenic role of LINC00511 in ER-negative tumorigenesis. ER insufficiency enhanced TFAP-2 activity at particular promoter regions, promoting LINC00511 expression. By interacting with EZH2 to attract PRC2 to regulate histone methylation, the ER-negative-associated LINC00511 repressed the expression of CDKN1B, assisting in the G1/S transition to maintain cellular growth.

Role of LINC00511 in breast cancer.

Cancer type Expression/Role Samples/Assessed cell lines Pathways Targets/Regulators Function Ref
Breast Cancer (BC) Upregulated/Oncogene 39 cases of breast cancer/MCF-10A, MDA-MB-468, MDA-MB-231, MDA-MB-453, MCF-7 miR-185-3p/E2F1/Nanog axis miR-185-3p/E2F1 LINC00511/miR-185-3p/E2F1/Nanog axis has a role in breast cancer stemness and malignancy Lu et al. (2018)
Upregulated/Oncogene 10 TNTPs/MDA-MB-231, MCF-7 LINC00511/miR-150/MMP13 axis miR-150/MMP13 The LINC00511/miR-150/MMP13 axis could represent a novel treatment strategy for sufferers with breast cancer, because it is a breast cancer promoter Shi et al. (2021)
Upregulated/Oncogene MDA-MB-231, MCF-7, T47D, MDA-MB-468, MCF-10a - MET, E2F2, TGFA, and WNT10A Patients with breast cancer who express LINC00511 more than usual have a bad outcome. Breast cancer progression is facilitated by LINC00511 Liu et al. (2021a)
Upregulated/Oncogene 21 TNTPs/MDA-MB-231, MCF-7, Hs-578T, T47D, MCF-10A LINC00511/miR-29c/CDK6 axis miR-29c/CDK6 Through controlling the miR-29c/CDK6 axis, LINC00511 lowering increased paclitaxel cytotoxicity in BC cells. A viable BC therapeutic option might be LINC005111 Zhu et al. (2019)
Upregulated/Oncogene 25 patients and 25 control samples LINC00511/miR-185-3p axis miR-301a-3p A more accurate diagnosis of BC may be made using serum LINC00511 and miR-301a-3p as prospective molecular indicators Mahmoud et al. (2021)
Upregulated/Oncogene MDA-MB-231, MDA-MB-436 LINC00511/miR-185/STXBP4 axis miR-185/STXBP4 Inhibition of LINC00511 reduces It has ability to bind competitively to miR-185, which boosts STXBP4 production and enhances radiation responsiveness in BC. A prospective treatment approach for boosting the prognosis of BC is the LINC00511/miR-185/STXBP4 axis Liu et al. (2019)
Upregulated/Oncogene - Apoptosis pathway - Through the suppression of antiapoptotic genes, LINC00511 deletion procedures using CRISPR/Cas9 improved the apoptosis of breast cancer cells Azadbakht et al. (2022)
Upregulated/Oncogene MCF7, UACC-812, MDA-MB-231 - EZH2 and CDKN1B In ER-negative breast cancer, lncRNAs have a role in controlling the network of cell cycle regulation, and this has led to speculation that LINC00511 may be used as an anticancer treatment Zhang et al. (2019)
Upregulated/Oncogene 15 TNTPs LINC00511/hsa-miR-573/GSDMC axis miR-573/GSDMC The most probable ncRNA-related mechanisms that drive GSDMC in BRCA are thought to be the LINC00511/hsa-miR-573 axis Sun et al. (2022)
Upregulated/Oncogene 7 TNTPs (HER-2-enriched) - - A putative chemical indicator and viable treatment option for breast cancer of the HER-2-enriched subgroup is LINC00511 Yang et al. (2016)
Gastric cancer

LINC00511 has been shown to promote progression of gstaric acnecr through regulating SOX4 expression and epigenetically suppressing PTEN to induce activity of PI3K/AKT pathway (Wang et al., 2021). Moreover, LINC00511 can promote growth of gastric tumors through acting as a molecular sponge for miR-124-3p and regulating expression of PDK4 (Sun et al., 2020a). miR-515-5p is another miRNA that is sponged by LINC00511 in gastric cancer cells leading to enhancemnet of proliferation and invasion of these cells (Wang et al., 2020a). Finally, miR-625-5p/NFIX (Chen et al., 2019a), miR-124-3p/EZH2 (Huang et al., 2020), miR-625-5p/STAT3 (Cui et al., 2021) and miR-29b/KDM2A (Zhao et al., 2020) are other molecular axes regulated by LINC00511 in gastric cancer. Table 2 shows the role of LINC00511 in gastric cancer.

Role of LINC00511 in gastric cancer.

Cancer type Expression/Role Samples/Assessed cell lines Pathways Targets/Regulators Function Ref
Gastric Cancer (GC) Upregulated/Oncogene AGS, HGC‐27, ACP01, SNU‐1, Het‐1A PI3K/AKT pathway miR‐195‐5p/SOX4 After epigenetically suppressing PTEN to activate the PI3K/AKT pathway by engaging EZH2, SOX4-induced LINC00511 stimulated SOX4 via ceRNA pattern, promoting GC cell proliferation, migration and stemness while preventing GC cell death Wang et al. (2021)
Upregulated/Oncogene MKN-45, BGC-823, HGC-27, MGC-803, GES-1 LINC00511/miR-124-3p/PDK4 axis miR-124-3p/PDK4 By functioning as a ceRNA to control the miR-124-3p/PDK4 axis, which could be a viable therapeutic option for GC, LINC00511 encourages the tumor cell growth Sun et al. (2020a)
Upregulated/Oncogene 25 patients with gastric cancer/GES-1, AGS, SGC7901, BGC823, MKN45, MGC803 MAPK signaling pathway miR-515-5p By influencing miR-515-5p, LINC00511 can stimulate the expansion of tumor cells, suggesting that it might be a viable option for the creation of anti-cancer medications Wang et al. (2020a)
Upregulated/Oncogene 35 TNTPs/GES1, GC27, BGC823, MGC803, SGC7901 LINC00511/miR-625-5p/NFIX axis miR-625-5p/NFIX By targeting NFIX in GC cells, LINC00511 is a tumor activator to sponge miR-625-5p. Elimination of this lncRNA might be viewed as a treatment option for GC therapy Chen et al. (2019a)
Upregulated/Oncogene 80 patients with GC/GES-1, MGC, HGC, MKN25, MKN28 LINC00511/miR-124-3p/EZH2 pathway miR-124-3p/EZH2 pathway In sufferers with GC, LINC00511 is linked to a poor overall survival. It was predicted that LINC00511 would be a suitable target for treating human GC since it has a function in encouraging the cancerous cells growth Huang et al. (2020)
Upregulated/Oncogene 50 TNTPs/MKN28, BGC-823, MKN-45, MGC-803, SGC-7901, GES-1 STAT3 signal pathway miR-625-5p/STAT3 By controlling miR-625-5p and STAT3, LINC00511 encourages GC cell growth, implying that LINC00511 has oncogenic capabilities that influence the formation of GC. Cui et al. (2021)
Upregulated/Oncogene AGS, SGC7901 LINC00511/miR-29b/KDM2A axis miR-29b/KDM2A axis In GC, LINC00511 depletion boosted the apoptosis and hindered cell growth. It is possible to exploit the LINC00511/miR-29b/KDM2A axis as a viable treatment option for GC. Zhao et al. (2020)
Lung cancer

LINC00511 has ben shown to promote proliferation, invasive capacities, and migration of non-small cell lung cancer cells through regulating miR-625-5p/GSPT1 axis (Cheng et al., 2021). Moreover, LINC00511 can promote progression of this type of cancer through binding to EZH2 and LSD1 and decreasing expression levels of LATS2 and KLF2 (Zhu et al., 2019). Besides, this lncRNA has a role in induction of tumor recurrence in this type of cancer through sponging miR-98-5p and increasing expression of TGFBR1 (Li et al., 2022). LINC00511 can also induce resistance of lung cancer cells to cisplatin through sponging miR-625 and influencing expression of LRRC8E (Liu et al., 2022). Finally, this lncRNA exerts its oncogenic effects in lung cancer through binding to EZH2 and decaresing expression of p57 (Sun et al., 2016). Table 3 shows the role of LINC00511 in lung cancer.

Role of LINC00511 in lung cancer.

Cancer type Expression/Role Samples/Assessed cell lines Pathways Targets/Regulators Function Ref
Lung Squamous Cell Carcinoma (LUSC) Upregulated/Oncogene SK-MES-1, H226, 16-HBE LINC00511/miR-150-5p/TADA1 axis miR-150-5p/TADA1 A plan for the therapeutic targeting of LINC00511 in LUSC should be developed, because it stimulates the advancement of LUSC. Wu et al. (2020)
Lung Adenocarcinoma (LUAD) Upregulated/Oncogene 45 LAC tissues and corresponding adjacent normal lung tissues/BEAS‐2B, H1299, A549 PKM2 signaling pathway miR-625-5p/PKM2 By influencing miR-625-5p/PKM2, LINC00511 was found to be engaged in the evolution of LAC, demonstrating that LINC00511/miR-625-5p/PKM2 may represent interesting treatment targets for LUAC. Xue and Zhang (2020)
Upregulated/Oncogene 40 TNTPs/A549, Calu-3, BEAS-2B, DV-90, PC-9 LINC00511/miR-195-5p/GCNT3 axis miR-195-5p/GCNT3 By suppressing miR-195-5p, LINC00511 reduction encourages GCNT3 production, and as a result, supports the malignant growth of LUAD. Zhang et al. (2022)
Upregulated/Oncogene A549/DDP, 16HBE LINC00511/miR-182/BIRC5 axis miR-182-3p/BIRC5 After injection of cisplatin (DDP), LINC00511 silencing prevents the growth of A549/DDP cells into tumors. In order to understand the mechanism of gained DDP tolerance, this research offers a unique LINC00511/miR-182/BIRC5 model Zhu et al. (2022)
Upregulated/Oncogene 35 TNTPs/A549, PC9, BEAS-2B Linc00511/miR-126-5p/miR-218-5p/COL1A1 axis, PIK3/AKT pathway miR-126-5p, miR-218-5p/COL1A1 By targeting miR-126-5p and miR-218-5p, LINC00511 influences COL1A1 production, encouraging cancerous cell growth and motility. LINC00511 could be a viable treatment approach for LUAD. Wang et al. (2022)
Other types of cancers

Over-expression of LINC00511 has been reported in a variety of cancers including colorectal, pancreatic, liver, thyroid and other types of cancers (Table 4).

Dysregulation of LINC00511 in different cancers (TNTP: tumor and non-tumor pairs of tissues).

Cancer type Expression/Role Samples/Assessed cell lines Pathways Targets/Regulators Function Ref
Hepatocellular Carcinoma (HCC) Upregulated/Oncogene Huh7, Hep3B - RAB27B There seems to be a link between the creation of invadopodia and the generation of exosomes and LINC00511 dysregulation. In HCC, LINC00511 could be a treatment option Peng et al. (2021)
Upregulated/Oncogene SMCC7721, HepG2, Huh7, Hep3B LINC00511/miR195/EYA1 axis miR195/EYA1 A prospective therapeutic option for the detection of HCC has been provided by LINC00511 that interacted with EYA1 to accelerate HCC formation through miR-195 Hu et al. (2020a)
Upregulated/Oncogene 127 TNTPs/LO2, Hep3B, HepG2, SMMC-7721, MHCC97H, Huh7, HCCLM3 - miR-424 LINC00511 may have a significant impact on how HCC develops, and that it will also act as a viable prognostic and therapeutic target. Wang et al. (2019a)
Liver Hepatocellular Carcinoma (LIHC) Upregulated/Oncogene LO2, MHCC-97H, Huh7, HCC-LM3, Hep3B, MHCC-97L, Huh6 - miRNA-29c Through boosting tumor cell proliferative ability, LINC00511 worsens LIHC’s development. A predictive marker for LIHC could be LINC00511 Liu et al. (2019)
Osteosarcoma (OS) Upregulated/Oncogene 24 TNTPs/SW1353, U2OS LINC00511/miR-185-3p/E2F1 axis miR-185-3p/E2F1 As an oncogenic RNA, LINC00511 leads to the formation and spread of tumor cells. The LINC00511/miR-185-3p/E2F1 axis may be extremely important for the onset of osteosarcoma Xu et al. (2020)
Upregulated/Oncogene 30 TNTPs s/(MG‐63, Saos‐2, U2OS, HOS, NHOst - miR‐765 Via substantially controlling the production of miR-765, aberrant transcription of LINC00511 boosted osteosarcoma cell tumorigenesis and motility Yan et al. (2018)
Downregulated/Tumor suppressor gene 45 patients with osteosarcoma/hFOB1.19, MG-63, U‐2OS, Saos‐2, HOS - - Elevated amounts of LINC00511 slow the growth of tumors. LINC00511 could be a new indicator and prospective osteosarcoma treatment approach Qiao et al. (2020)
Upregulated/Oncogene 10 TNTPs/hFOB 1.19, MG-63, HOS, Saos-2, 143B LINC00511/miRNA- 618/MAEL axis miRNA- 618/MAEL OS cell growth and malignancy were both hindered by lower LINC00511 production. It could be a viable biomarker for more exploration on the treatment of OS. Guo et al. (2019)
T-cell Acute Lymphoblastic Leukemia (T-ALL) Upregulated/Oncogene Blood samples of 35 T-ALL patients and 30 normal controls/HPB-ALL, TALL-1, ALL-SIL, CUTLL1, PBMC LINC00511/miR-195-5p/LRRK1 axis miR-195-5p/LRRK1 Through the miR-195-5p/LRRK1 axis, LINC00511 accelerated the evolution of T-ALL, pointing a possible therapeutic hint for the T-ALL sufferers Li et al. (2020)
Glioma Upregulated/Oncogene HEB, NHA, T98 G cells (CRL-1690), A172 cells (CRL-1620), LN229 cells (CRL-2611), U-87MG cells (HTB-14IG) LINC00511/miR-15a-5p/AEBP1 axis miR-15a-5p/AEBP1 Glioma formation can be slowed down by LINC00511 knockdown. Additionally, via the miR-15a-5p/AEBP1 axis, the process of LINC00511 influences the onset of glioma Liu et al. (2021b)
Upregulated/Oncogene U87, U251, SHG44, A172, NHA SP1/LINC00511/miR‐124‐3p/CCND2 axis miR‐124‐3p/CCND2 The transcription factor SP1 served as the inspiration for the overexpression of LINC00511 in glioma cells. Additionally, the upregulation of LINC00511 competitively sponges the miR-124-3p, driving the production of CCND2 and the cyclin D2 protein produced by this gene, which may hold significant potential for glioma therapies Li et al. (2019)
Papillary Thyroid Carcinoma (PTC) Upregulated/Oncogene 41 TNTPs/B-CPAP, KTC-1, KTC-1 - CDKs and EZH2 As an oncogene in PTC, LINC00511 promotes proliferation through CDKs. It will serve as a fundamental therapeutic target for PTC. Xiang et al. (2020)
Colorectal Cancer (CRC) Upregulated/Oncogene 85 CRC tissues and adjacent normal tissues/HCT116, HT-29, LoVo, SW480, SW620, NCM460 HNF4α/LINC00511/IL24 axis HNF4α and IL24 The proliferative, spreading and aggressive features of CRC cells are lowered by LINC00511 reduction, that eventually reduces tumorigenicity of CRC. Lu et al. (2021)
Upregulated/Oncogene 120 TNTPs/SW480, SW620, HCT16, HT29, NCM460 LINC00511-mediated microRNA (miR)-625-5p/WEE1 axis miRNA-625-5p/WEE1 By suppressing WEE1 and restoring miR-625-5p, downregulated LINC00511 prevents the carcinogenesis of CC, establishing a fundamental standard for CC-targeted treatment Qian et al. (2022)
Upregulated/Oncogene 12 TNTPs/HT-29, HCT8, HCE8693, SW620, NCM460 LINC00511/miR-29c-3p/NFIA axis miR-29c-3p/NFIA By inhibiting the LINC00511/miR-29c-3p/NFIA axis, LINC00511 assisted in the onset of CRC, proposing that LINC00511 could be a viable therapeutic target. Hu et al. (2020b)
Glioblastoma (GBM) Upregulated/Oncogene 160 TNTPs/U87, A172, U138, U251, U373, LN‐18, T98G, Human HEK293T Wnt/β-catenin signaling miR‐126‐5p In GBM cells, LINC00511 controlled Wnt/Catenin stimulation by functioning as a molecular sponge for miR-126-5p. It stated that LINC00511 could operate as a marker for the treatment of GBM. Wang et al. (2021)
Upregulated/Oncogene 36 GBM tissues and 8 non-tumour brain tissues (NBT)/U87, LN229, U251, A172, 293T LINC00511/miR‐524‐5p/YB1/ZEB1 axis miR‐524‐5p/YB1 By boosting EMT, the LINC00511/miR524-5p/YB1/ZEB1 positive feedback loop might encourage GBM cell motility and infiltration. LINC00511 could be a viable therapeutic target for GBM sufferers Du et al. (2020)
Esophageal Cancer (ECa) Upregulated/Oncogene - - miR-150-5p By attaching to miR-150-5p and sponging this miRNA, LINC00511 controls the creation of cancerous cells and, could be a treatment option for ECa Sun et al. (2020a)
Cervical Cancer (CC) Upregulated/Oncogene - LINC00511/miR-497-5p/MAPK1 axis miR-497-5p/MAPK1 Overexpression of LINC00511 boosted CC cell growth, motility and infiltration, whereas LINC00511 reduction had the opposite effects Lu et al. (2022)
Upregulated/Oncogene 92 cervical cancer tissues and 40 adjacent normal tissues/SiHa, HeLa, C33A, Caski, Ect1/E6E7 - - In cervical cancer sufferers, high LINC00511 transcription is linked to clinical deterioration. The growth, motility and infiltration of tumor cells are restricted by LINC00511 suppression Yu et al. (2019)
Upregulated/Oncogene 40 TNTPs/HT29, LOVO, SW620, SW480 LINC00511/miR-153-5p/HIF-1α axis miR-153-5p/HIF-1α A crucial part of the CRC carcinogenesis is played by LINC00511. HIF-1α/LINC00511/miR-153-5p might be used as a therapeutic target in CRC. Sun et al. (2020b)
Upregulated/Oncogene 19 TNTPs/SiHa, CaSki, C33A, HUCEC LINC00511/miR-324-5p/DRAM1 axis miR-324-5p/DRAM1 The miR-324-5p/DRAM1 axis is regulated by LINC00511, acting as a ceRNA which, promotes the progression of both HPV-negative and HPV-positive cervical cancer Zhang et al. (2020)
Upregulated/Oncogene 84 CC patients/PTX-resistant Hela/PTX - - Suppression of LINC00511 may lessen CC cell motility and infiltration as well as paclitaxel tolerance, and may boost cell death in CC cells. LINC00511 suppression offers CC a brand-new treatment option Mao et al. (2019)
Upregulated/Oncogene 47 TNTPs/SiHa, CaSki, C33A, ME180, HeLa, NCECs - RXRA or PLD1 In CC, LINC00511 promotes the production of PLD1, which is controlled by RXRA. It could be a viable indicator for the therapy of CC. Shi et al. (2020)
Cervical Squamous Carcinoma (CESC) Upregulated/Oncogene 115 cases of CESC, 79 cases of cervical intraepithelial neoplasia and 101 healthy controls - - A diagnostic model consisting of CCAT2 and LINC01133 has exhibited significant clinical utility for the identification of cervical intraepithelial neoplasia in both healthy individuals and patients. The serum concentrations of CCAT2, LINC01133 and LINC00511 could be used as effective non-invasive indicators for the diagnosis of CESC. Wang et al. (2020b)
Clear Cell Renal Cell Carcinoma (ccRCC) Upregulated/Oncogene 49 TNTPs/HK-2, A498, 786-O, ACHN, Caki-2 LINC00511/miR-625/CCND1 pathway miRNA-625/cyclin D1 As a ceRNA, LINC00511 controls the transcription of CCND1 in ccRCC via sponging miR-625. As a result, the LINC00511/miR-625/CCND1 pathway could offer ccrCC patients a prospective treatment approach Deng et al. (2019)
Bladder Cancer (BcA) Upregulated/Oncogene 47 TNTPs/TCCSUP, SW780 LINC00511/miR-143-3p/PCMT1 axis miR-143-3p/PCMT1 By suppressing the production of miR-143-3p and promoting the production of PCMT1, LINC00511s molecular mechanism may prevent bladder cancer cells from proliferating and invading. A novel target for bladder cancer treatment may be offered by LINC00511 Dong et al. (2021)
Upregulated/Oncogene 45 TNTPs/SV-HUC-1, BIU87, T24, 5637 Wnt/β-catenin signaling pathway miR-15a-3p By inhibiting the Wnt/β-catenin signaling pathway activity, LINC00511 suppression decreases bladder cancer cells ability to proliferate and increases their likelihood of dying. LINC00511 could also be a putative bladder cancer indicator and possible therapeutic target. Li et al. (2018)
Tongue Squamous Cell Carcinoma (TSCC) Upregulated/Oncogene Tca-8113 LINC00511/miR-765/LAMC2 axis miR-765/LAMC2 By sponging miR-765 with ceRNA, LINC00511 increases the production of LAMC2. the ceRNA regulation network contributes to new knowledge about the pathophysiology of TSCC and given information on how to take advantage of the emerging area of lncRNA-directed treatment for TSCC. Ding et al. (2018)
Non-small Cell Lung Cancer (NSCLC) Upregulated/Oncogene 67 patients/16HBE, A549, NCIH1299, NCIH1650, NCIH 1975, NCIH460 LINC00511/miR-625-5p/GSPT1 axis miR-625-5p/GSPT1 By targeting miR-625-5p/GSPT1, LINC00511 boosts NSCLC cell growth, infiltration and motility. LINC00511 is a possible diagnostic indicator and treatment option for NSCLC. Cheng et al. (2021)
Upregulated/Oncogene 57 TNTPs - EZH2 and LSD1/LATS2 and KLF2 Apoptosis is triggered in NSCLC cells when LINC00511 is knocked down, although this reduces the capability of the cells to spread and infiltrate Zhu et al. (2019)
Upregulated/Oncogene 62 stage I NSCLC patients and the age- and gender-matched healthy controls LINC00511/miR-98-5p/TGFBR1 axis miR-98-5p/TGFBR1 In NSCLC, LINC00511 quantities were raised, which may contribute to distant postoperative recurrence of NSCLC and enhance NSCLC cell growth, motility and penetration by targeting and controlling the miR-98-5p/TGFBR1 axis Li et al. (2022)
Upregulated/Oncogene 40 TNTPs/A549, H522, A549/DDP, H522/DDP, BEAS-2B LINC00511/miR-625/LRRC8E pathway miR-625/LRRC8E LINC00511 enhanced LRRC8E production by downregulating miR-625 to boost DDP tolerance in NSCLC. A viable therapeutic target to reduce DDP tolerance in NSCLC is LINC00511 Liu et al. (2022)
Upregulated/Oncogene 124 TNTPs/A549, SK-MES-1, H1299, 95D, H460, H520, H1975, H157, SK-LU-1, SPC-A-1, 16HBE - EZH2 and p57 In NSCLC, LINC00511 is clinically, physiologically and molecularly oncogenic Sun et al. (2016)
Pancreatic Cancer (PC) Upregulated/Oncogene 91 TNTPs/BxPC-3, CFPAC-1, PANC-1, SW 1990, MIAPaCa-2, HPDE6-C7 LINC00511/miR-370-5p/p21 Axis miR-370-5p/p21, Snail, and ZEB1 The LINC00511/miR-370-5p/p21 promoter region axis was responsible for the suppressive impact of DET (deoxyelephantopin) on the growth and spread of PC cells Ji et al. (2022)
Pancreatic Ductal Adenocarcinoma (PDAC) Upregulated/Oncogene 140 TNTPs, PANC‐1, MIA PaCa‐2, Capan‐2, SW 1990, ASPC‐1, BxPC‐3, HPDE6 LINC005/hsa‐miR29b‐3p/VEGFA axis miR‐29b‐3p/VEGFA The etiology of PDAC is profoundly influenced by the new lncRNA LINC00511. LINC00511 is a unique predictive indicator that can forecast the clinical outcomes of PDAC sufferers following surgery and could be used as a treatment option for PDAC. Zhao et al. (2018)
Thyroid Carcinoma (TC) Upregulated/Oncogene TPC-1, BCPAP, IHH-4, Nthy-ori 3–1 JAK2/STAT3 signaling pathway and LINC00511/TAF1/JAK2 axis TAF1 and JAK2 Through TAF1-mediated JAK2/STAT3 signaling, enhanced expression of LINC00511 increased the radiosenitivity of TC cells. The potential biomarker function of LINC00511 in the management of TC was shown by the recent research Chen et al. (2019b)
Ovarian Cancer (OC) Upregulated/Oncogene CAOV3, OVCAR3, SKOV3, UWB1.289 - miR-424-5p and miR-370-5p/ESR1 With the suppression of cell death, upregulated LINC00511 boosted the vitality, motility and penetration of CAOV3 cells. The disruption of miR-424-5p and miR-370-5p is likely responsible for these actions that promote malignancy Wang et al. (2019b)
Upregulated/Oncogene SKOV3, SNU840 - EZH2 and P21 The growth of OC cells is slowed by LINC00511 silencing. This information may offer a valuable lncRNA as a predictive indicator and possible treatment option Deng et al. (2019)
Transcriptional regulation of LINC00511

Investigations in the Hormonizome database (Rouillard et al., 2016) indicated that 18 transcription factors (CTCF, EP300, ESR1, EZH2, FOXA1, GATA3, H2AFZ, MAX, MYC, NFIC, NR2F2, NR3C1, POLR2A, RAD21, TCF12, TEAD4, YY1, and ZBTB7A) possibly bind to the promoter of LINC00511 gene based on ChIP-seq data from the ENCODE Transcription Factor Target dataset.

 LINC00511 related pathways and functions.

Based on lncHUB database (https://maayanlab.cloud/lnchub/), 10 KEGG pathways with the highest Z-score in which LINC00511 is predicted to be involved include glycosphingolipid biosynthesis, bacterial invasion of epithelial cells, basal cell carcinoma, central carbon metabolism in cancer, notch signaling pathway, RNA polymerase, DNA replication, cell cycle, bladder cancer and mismatch repair. Additionally, 10 gene ontology (GO) terms with the highest Z-score that are associated with LINC00511 include regulation of hydrogen peroxide-induced cell death (GO:1903205), negative regulation of response to reactive oxygen species (GO:1901032), protein heterotetramerization (GO:0051290), viral release from host cell (GO:0019076), exit from host cell (GO:0035891), signal complex assembly (GO:0007172), regulation of striated muscle tissue development (GO:0016202), regulation of myelination (GO:0031641), positive regulation of kidney development (GO:0090184) and regulation of proteolysis (GO:0030162). Also, IGSF11, PHLPP1, CPOX, SOX2, PACC1, SOX21, TMPRSS5, HEY1, MARCKS, KCTD5, OLIG2, ATAT1, CDK5R1, BCAN and BAALC are 15 genes with the highest Z-score predicted to be co-expressed with LINC00511.

 LINC00511 interactions with miRNAs and other molecules

Based on RNAInter (RNA Interactome Database) (Kang et al., 2022), LINC00511 has interactions with hsa-miR-29b-3p, hsa-miR-765, hsa-mir-150, miR-1231, TFAP2A-AS2, hsa-miR-185-3p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, RAD51-AS1 and EZH2 with score ≥0.1. Also, based on LncRNA2Target v3.0 (Cheng et al., 2019), LINC00511 interactions with miRNAs has been showed in Table 5.

LINC00511 interactions with miRNAs.

Target gene LncRNA experiment Tissue Cell line Disease state Reference
MIR29B1 Luciferase reporter assays, RNA immunoprecipitation Pancreatic cancer PANC-1, MIA PaCa-2, Capan-2, SW 1990, ASPC-1, BxPC-3 Pancreatic cancer Zhao et al. (2018)
MIR765 Dual luciferase reporter assays NA Tca-8113 Tongue squamous cell carcinoma Ding et al. (2018)
MIR524 Dual-luciferase gene reporter assay, RNA immunoprecipitation (RIP) Brain U87, LN229, U251, A172, 293T Glioblastoma Multiforme Du et al. (2020)
miR-124-3p Luciferase assay GC tissue GES-1, MGC, HGC, MKN25, MKN28 Gastric cancer Huang et al. (2020)
MIR150 Luciferase reporter assay Breast MDA-MB-231, MCF-7 Breast Cancer Shi et al. (2021)
Impact of LINC00511 dysregulation on clinical outcome of patients with cancers

We investigated the survival rate caused by LINC00511 in different cancers using ualcan database (Chandrashekar et al., 2017). This database performs survival analysis using TCGA data. The difference was statistically significant with a log-rank p-value less than 0.05. As a result, LINC00511 has an effect on the survival rate of patients with adrenocortical carcinoma (ACC), breast invasive carcinoma (BRCA), kidney renal clear cell carcinoma (KIRC), acute myeloid leukemia (LAML), liver hepatocellular carcinoma (LIHC), Mesothelioma (MESO), pheochromocytoma and paraganglioma (PCPG) and sarcoma (SARC) (Figure 3). While in patients with LAML, overexpression of this lncRNA is associated with better clinical outcome, in other types of cancers, its upregulation is associated with lower survival.

The impact of LINC00511 on survival of patients with different cancers.

 Discussion

LINC00511 is a lincRNA being over-expressed in a variety of human tumors and cancer cell lines. Except for a single study in osteosarcoma (Qiao et al., 2020), other studies in this type of cancer and other cancers have reported upregulation of LINC00511 in tumoral tissues compared with their non-tumoral counterparts. Dysregulation of LINC00511 affects cancer pathogenesis through increasing cell proliferation and inhibiting cell apoptosis. It can also increase activity of several cancer-promoting signaling pathways.

A previous meta-analysis has reported association between over-expression of LINC00511 and poor prognosis in different cancers in terms of overall, progression-free or relapse-free survival times (Agbana et al., 2020). Moreover, upregulation of this lncRNA has been associated with larger tumor size, recurrent disorder and metastasis to lymph nodes or distant organs (Agbana et al., 2020).

Mechanistically, LINC00511 can act as a molecular sponge for a variety of miRNAs regulating their targets. miR-185-3p/E2F1, miR-150/MMP13, miR-29c/CDK6, miR-185/STXBP4, miR-573/GSDMC, miR‐195‐5p/SOX4, miR-124-3p/PDK4, miR-625-5p/NFIX, miR-124-3p/EZH2, miR-625-5p/STAT3, miR-29b/KDM2A, miR-195/EYA1, miR-185-3p/E2F1, miRNA-618/MAEL, miR-195-5p/LRRK1, miR-15a-5p/AEBP1, miR‐124‐3p/CCND2, miRNA-625-5p/WEE1, miR-29c-3p/NFIA, miR-150-5p/TADA1, miR‐524‐5p/YB1, miR-625-5p/PKM2, miR-195-5p/GCNT3, miR-182-3p/BIRC5, miR-218-5p/COL1A1, miR-497-5p/MAPK1, miR-153-5p/HIF-1α, miR-324-5p/DRAM1, miR-625/cyclin D1, miR-143-3p/PCMT1, miR-765/LAMC2, miR-625-5p/GSPT1, miR-98-5p/TGFBR1, miR-625/LRRC8E, miR-370-5p/p21, miR‐29b‐3p/VEGFA and miR-370-5p/ESR1 are examples of miRNA/mRNA axes that are regulated by LINC00511. Molecular axes being regulated by LINC00511 in more than one type of cancer represent better targets for design of anti-cancer therapies since they can be applied in a wider range of malignancies. Therefore, identification of the impact of above-mentioned molecular axes in the progression of different types of cancer is an important step in design of novel therapeutics.

LINC00511 can induce stemness in cancers and facilitate tumor progression and metastasis (Lu et al., 2018). Therefore, LINC00511-modifying modalities can be used as possible strategies for defeating cancer metastasis.

The prognostic role of over-expression of LINC00511 in different cancers has been evaluated thoroughly by various research groups indicating its important effects on survival of affected individuals. Future studies should assess its expression in biofluids to provide a non-invasive route for cancer diagnosis and patients’ follow-up.

 Author contributions

MT designed and supervised the study. SG-F wrote the draft and revised it. AS, BH, and SA collected the data and designed the figures and tables. All the authors read the submitted version and approved it.

 Funding

This study was Financially supported by Shahid Beheshti University of Medical Sciences.

 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.

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