In the United States, AML accounts for approximately one-third of all leukemias diagnosed and 1.2% of all annual new cancer diagnoses (Pelcovits and Niroula, 2020) The role of LINC00467 in AML pathogenesis was recently researched by Lu et al. (2021) The results of this study showed that LINC00467 expression was associated with the malignant phenotypes of AML cells and that it acted as a ceRNA of miR-339. SKI is a gene regulated by miR-339 that has been reported to promote AML development. Further investigation of the underlying mechanism verified that treatment with a miR-339 inhibitor largely diminished the influence of LINC00467 knockdown on AML cells. These results suggest that targeting the LINC00467/miR-339/SKI axis could be a suitable approach for the treatment of AML.

NSCLC accounts for nearly 85% of lung cancers (Herbst et al., 2008; Yin et al., 2018) and is known to be the most common cause of cancer-related death worldwide. (Siegel et al., 2018) Most of the patients diagnosed with NSCLC are already in advanced stages for which effective treatment options are still lacking (Hayden and Ghosh, 2008; Saha et al., 2020) LINC00467 regulates ERK1/2 signaling in NSCLC. Inhibiting SIRT6 and blocking the ERK1/2 signaling pathway lead to the upregulation of miR-125a-3p and the downregulation of LINC00467 in NSCLC cells. Additionally, LINC00467 upregulation or miR-125a-3p downregulation exacerbated the malignant phenotypes and DDP resistance in NSCLC cells. (Xue et al., 2021).

LUAD is the commonest histological subtype of NSCLC. Early diagnosis of LUAD is particularly difficult and it is prone to metastasize, as a result of which it is associated with a poor prognosis. (Yang et al., 2019) LINC00467 was found to be upregulated in human LUAD tumor tissues and its expression level was found to correlate with the clinical severity of LUAD. Functional in vitro experiments indicated that LINC00467 promoted LUAD cell proliferation, migration, and invasion and suppressed apoptosis. Furthermore, some miRNAs sponged by LINC00467 and their downstream targets, which play a role in LUAD development, have been reported. For instance, a study found that LINC00467 can suppress apoptosis and promote proliferation and stemness of LUAD cells by sponging cytoplasmic miR-4779 or miR-7978. (Chang and Yang, 2019) Additionally, Ding et al. (2019) reported that LINC00467 promotes proliferation in LUAD cells by upregulating the expression level of CCND1, a primary regulator of the cell cycle, via sponging miR-20b-5p.

Finally, Wang et al. reported that LINC00467 DNA copy number amplification contributed to its overexpression and was positively associated with distant metastasis, immune infiltration, and poor overall survival in LUAD. In addition, LINC00467 overexpression partly originated from its DNA demethylation. Based on microarray analysis and bioinformatics, this study revealed a comprehensive miRNAs-mRNAs network that included two microRNAs (hsa-miR-1225-5p, hsa-miR-575) and five mRNAs (BARX2, BCL9, KCNK1, KIAA1324, TMEM182) specific to LINC00467 in LUAD. Through bioinformatic analysis, two potential prognostic biomarkers (BARX2 and BCL9) for LUAD were revealed. (Wang et al., 2021) Based on the results of these reports, LINC00467 stands as a potential diagnostic and prognostic biomarker, as well as a suitable therapeutic target for LUAD.

In the developing world, cervical cancer remains the second most common cancer among women, thereby placing a heavy economic burden on society.(Hillmann et al., 2013; Siva et al., 2015) It has been reported that cytoplasmic LINC00467 plays an important role in the progression of cervical cancer by competitively sponging miR-107 to downregulate the expression of the downstream gene KIF23. LINC00467 silencing or miR-107 overexpression inhibited cervical cancer cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and tumorigenic ability in vivo, further suggesting that targeting LINC00467 may be a novel therapeutic strategy for patients with cervical cancer. (Li et al., 2019).

HCC is a prevalent human malignancy with high morbidity and mortality worldwide.(Maluccio and Covey, 2012; Laursen, 2014) Exploring novel therapeutic targets for HCC remains a pressing challenge nowadays (Dhar et al., 2018; Andrade et al., 2019) LINC00467 expression is upregulated in HCC cells and is related to HCC progression. Additionally, miR-509-3p and platelet-derived growth factor receptor alpha (PDGFRA), which are targets of LINC00467, promoted proliferation and invasion, repressed apoptosis, and ameliorated the resistance to axitinib, the commonly-used drug for HCC (Chan et al., 2017; Li W. et al., 2021) Moreover, Zheng et al. described that silencing LINC00467 could modulate HCC cell growth and development by targeting the miR-18a-5p/NEDD9 axis. (Zheng et al., 2020) Interestingly, one study reported that the expression of LINC00467 was significantly decreased in HCC tissues, especially in metastatic HCC tissues, which is in contrast to the results of other relevant studies on LINC00467 in HCC. Furthermore, it was reported that LINC00467 exerted a tumor suppressor role by reducing cell viability, proliferation, migration, and invasion by regulating the miR-9-5a/PPARA signaling axis in HCC. (Cai et al., 2019).

OS, which mainly occurs in children and adolescents, has a poor prognosis and low survival rate due to its rapid progression and metastasis ability.(Wycislo and Fan, 2015; Marko et al., 2016) Ma et al. reported that LINC00467 expression was increased in OS cell lines, and that overexpression of LINC00467 increased cell proliferation, migration, and invasion, and decreased cell apoptosis by upregulating the expression of high mobility group A1 (HMGA1) by targeting miR-127 in OS. (Ma et al., 2020) Additionally, it was reported that LINC00467-mediated sponging of miR-127 also regulated the expression of karyopherin subunit α 4 (KPNA4), contributing to OS progression. (Yan et al., 2021).

CRC is the second leading cause of cancer-related mortality worldwide, partly due to the lack of effective treatments.(Walsh and Terdiman, 2003; Sunkara and Hébert, 2015; Sung et al., 2021) LINC00467 expression level has been reported to be significantly increased in CRC tissues and cell lines. Silencing its expression resulted in the inhibition of CRC cell proliferation, invasion, and EMT. (He et al., 2019) Another study using data from 31 CRC patients further elucidated that LINC00467 upregulation was closely associated with metastasis and TNM stage in CRC. Moreover, the authors reported that overexpression of miR-451a reduced the level of LINC00467 in CRC cells. (Bai et al., 2020) Additionally, LINC00467 has also been suggested to play other biological roles in CRC cells, including mediating chemoresistance to 5-FU and metastasis, through the miR-133b/ferritin light chain (FTL) axis. (Li et al., 2020).

PC, which is a heterogeneous disease, is the most common non-skin male malignancy in the Western world. (Haffner et al., 2021) LINC00467 expression is upregulated in PC tissues and cells. Meanwhile, LINC00467 knockdown reduced PC cell proliferation, migration, and invasion via regulation of the miR-494-3p/STAT3 axis. Additionally, it has also been shown that downregulation of LINC00467 inhibited M2 macrophage polarization and suppressed the migration and invasion of PC cells by activating the STAT3 pathway. These results suggest that inhibiting LINC00467 may be an effective therapeutic strategy for patients with PC. (Jiang et al., 2021).

Breast cancer is the most common type of malignancy among women and is associated with a high number of cancer-related deaths worldwide. (Jemal et al., 2011) Zhang et al. reported that silencing LINC00467 hindered the proliferation, migration, invasion, and EMT of breast cancer cell lines in vitro, whereas overexpression of LINC00467 predicted poor overall survival. Additional experiments have revealed that LINC00467 sponges miR-138-5p while directly interacting with LIN28B, a significant oncogene in breast cancer, to elevate its protein level. (Zhang et al., 2021).

ESCC, an important subtype of esophageal carcinoma, is the most common primary gastrointestinal malignant tumor. It has a relatively low 5-years survival rate and a high incidence, with more than 400,000 newly-diagnosed cases annually worldwide (Luo et al., 2019; Sugimura et al., 2019) LINC00467 expression is upregulated in ESCC tissues and cell lines, and high LINC00467 expression is correlated with the promotion of cell proliferation and inhibition of cell apoptosis. More importantly, LINC00467 facilitated ESCC progression by sponging miR-485-5p and modulating DPAGT1 levels. (Liu et al., 2021).

HNSCC, which mainly affects the oral cavity, pharynx, and larynx, is among one the ten malignancies with more than 600,000 new cases worldwide annually (Siegel et al., 2017; Xu et al., 2020) The notable upregulation of LINC00467 in HNSCC promotes cell growth, cell migration, and EMT by sponging miR-299-5p, thereby upregulating the expression of the oncogene tumor ubiquitin specific protease-48 (USP48), ultimately leading to HNSCC progression. (Chen and Ding, 2020) Additionally, Liang et al. reported that LINC00467 over-expression in HNSCC patients promoted cell invasion and inhibited apoptosis by sponging miR-1285-3p and modulating the expression level of TFAP2A, a downstream target of miR-1285-3p. (Liang et al., 2021).

GC is an aggressive malignant tumor with a high mortality rate that is often diagnosed at an advanced stage. (Abdi et al., 2020) A study found that LINC00467 knockdown inhibited proliferation, migration, and invasion of GC cells. Furthermore, researchers revealed that LINC00467 promotes GC progression by directly regulating miR-7-5p/EGFR (epidermal growth factor receptor) axis. (Deng et al., 2021).

Gliomas are tumors derived from the neuroepithelial ectoderm that stand among the most prevalent intracranial tumors, accounting for approximately 40% of all brain tumors. (Chen et al., 2017) Gao et al. demonstrated that high LINC00467 expression is a distinctive feature of glioma cell lines compared with normal cell lines. Moreover, LINC00467 was shown to promote the viability, migration, and invasion of glioma cells, and its expression level was negatively correlated with that of miRNA-200a, but positively correlated with E2F3 expression. LINC00467 accelerated the progression of gliomas by regulating the miR-200a/E2F3 axis. (Gao et al., 2020) Zhang et al. showed that increased LINC00467 expression in glioma cell lines promoted tumor proliferation, invasion, and cell cycle progression, but inhibited cell apoptosis by binding to DNMT1 to inhibit the expression of the tumor suppressor P53. (Zhang et al., 2020) In addition, another study found that LINC00467 exerted its biological function, including accelerating the proliferation and invasion abilities of glioma cells, as well as attenuating apoptosis, by sponging miRNA-485-5p (Jiang and Liu, 2020).

Glioblastoma, which is considered an advanced stage of glioma, is associated with a lower overall survival rate than glioma. (Zhang et al., 2019; Pelcovits and Niroula, 2020) LINC00467 knockdown was demonstrated to hinder cell proliferation while promoting cell apoptosis in glioblastoma by sponging miR-339-3p and regulating its target downstream gene, IP6K2. (Liang and Tang, 2020).

Neuroblastoma is a malignant embryonal tumor frequently diagnosed in children that usually occurs in the abdomen and has a high metastatic burden. (Park and Cheung, 2020) The role of LINC00467 in human cancers was first reported by Atmadibrata et al., who identified that LINC00467 transcription was regulated by N-Myc, a type of Myc oncoprotein that is associated with neuroblastoma occurrence. (Atmadibrata et al., 2014) In this study, it was demonstrated that N-Myc could reduce LINC00467 and RD3 gene promoter activity by directly binding to the Sp1-binding site-enriched region. Through this regulatory mechanism, N-Myc could downregulate the expression of LINC00467 and RD3. Moreover, LINC00467 could reduce the mRNA expression of its neighboring protein-coding gene RD3. To conclude, N-Myc-mediated suppression of RD3 mRNA expression could be blocked by N-Myc-mediated suppression of LINC00467. Furthermore, LINC00467 knockdown reduced the survival of neuroblastoma cells by inducing the expression of DKK1, a classic tumor suppressor gene. However, in this study, the specific roles of LINC00467 in neuroblastoma cells were not investigated in detail.

Bladder cancer, which mainly occurs in men, is the most common malignancy of the genitourinary system. (Bray et al., 2018) A recent study on the underlying molecular mechanisms of bladder cancer validated that LINC00467 is highly expressed in bladder cancer tissues and cells. LINC00467 was also demonstrated to be a promotion of bladder cancer cell proliferation and invasion. Using the catRAPID algorithm, it was predicted that LINC00467 could bind to NF-kB p65 through several binding sites. Further functional experiments showed that LINC00467 binding to NF-kB p65 increased the stability of this transcription factor and its nuclear translocation, a subcellular process in which NF-kB p65 could be transported into the cell nucleus to regulate gene expression. Moreover, rescue assays demonstrated that LINC00467 could promote the progression of bladder cancer through the NF-κB signaling pathway, which is closely correlated with the occurrence and development of tumors. (Xiao et al., 2021)

In LUAD, except for sponging miRNAs, LINC00467 could also exert its function through other molecular mechanisms. A study confirmed that LINC00467 inhibited the expression of HtrA serine peptidase 3 (HTRA3), a downstream gene of LINC00467, by recruiting EZH2 to the HTRA3 promoter, thereby regulating the characteristics of LUAD cells. (Wang et al., 2019) Yang et al. (2019) discovered that STAT1 (signal transducer and activator of transcription 1)-mediated upregulation of LINC00467 promoted LUAD cell proliferation and migration by recruiting enhancer of zeste homolog 2 (EZH2) to downregulate DKK1, which resulted in the inhibition of the Wnt/β-catenin signaling pathway.

In another study, Using the GEPIA and Kaplan–Meier Plotter databases, Zhu et al. found that LINC00467 is highly overexpressed in NSCLC tissues and is associated with advanced clinical stages and poor prognosis. Furthermore, functional experiments confirmed that LINC00467 upregulation was due to TDG (Thymine DNA Glycosylase)-mediated acetylation. Additionally, LINC00467 has been proven to promote NSCLC cell proliferation and metastasis by regulating the Akt signaling pathway. (Zhu et al., 2020).

LINC00467 can also regulate the initiation and development of HCC through interacting with certain proteins and participating in post-transcriptionally modification. Jiang et al. reported that upregulation of LINC00467 facilitated proliferation and metastasis but hindered cell apoptosis in HCC. A series of functional experiments revealed that the underlying mechanism relied on the direct binding between LINC00467 and insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3), which increased the stability of the transcript encoding the tumor necrosis factor receptor-associated factor 5 (TRAF5). (Jiang et al., 2020) In addition, LINC00467 can post-transcriptionally reduce the expression of the tumor suppressor NR4A3 by regulating Dicer-dependent RNA splicing, which ultimately contributes to HCC tumorigenesis. (Wang et al., 2020)

To date, there has only been one article of LINC00467 working by encoding a micro peptide. A study focusing on the role of ATP synthase-associated peptide (ASAP), a micro peptide encoded by LINC00467, reported that ASAP facilitated tumor proliferation through the regulation of mitochondrial ATP production in CRC. Moreover, ASAP expression was negatively correlated with the prognosis of patients with CRC. (Ge et al., 2021).

TGCTs, which can be classified as seminoma or non-seminoma tumors, mainly occur in men aged 20–40 years. In China, its incidence is one every 100,000 people. Furthermore, in China as well as worldwide, the incidence of this disease is gradually increasing (Chia et al., 2010; Greene et al., 2010; Shanmugalingam et al., 2013) Bo et al. reported that LINC00467 can promote TGCT cell migration and invasion by controlling the expression level of AKT3 and affecting the total AKT phosphorylation level. Interestingly, LINC00467 could also inhibit the infiltration of immune cells as well as their activation, indicating that it may be a potential target for anti-PD-1 immunotherapy. (Bo et al., 2021)

In GC, Xu et al. reported that the upregulation of LINC00467 in patients with GC was positively associated with tumor differentiation and the TNM stage. Functional experiments revealed that overexpression of LINC00467 increases GC cell viability and proliferation while suppressing apoptosis by enhancing ITGB3 (integrin subunit beta 3) levels. (Xu et al., 2021)