LINC00313 regulates the metastasis of testicular germ cell tumors through epithelial-mesenchyme transition and immune pathways

Abstract

Testicular germ cell tumor (TGCT) is a relatively rare entity tumor, accounting for only 1% of all male cancers. However, it is the most common solid tumor in young men between 15 and 34 years old. Long noncoding RNAs (lncRNAs) are involved in various physiological and pathological processes. However, the functions of lncRNAs in TGCT have only rarely been investigated. LncRNAs associated with TGCT were identified using Gene Expression Omnibus (GEO) database and UCSC XENA database data mining. The effects of LINC00313 on NCCIT cell migration and invasion were evaluated in transwell assays. The expression levels of epithelial-mesenchyme transition (EMT)-related proteins in cells knockdown of LINC00313 were analyzed by Western blot. Correlation analyses between lncRNA LINC00313 expression and copy number variation (CNV) and immune cell infiltration were carried out using The Cancer Genome Atl as (TCGA) data. The effect of Panobinostatin targeting LINC00313 in TGCT cells was investigated. We observed higher LINC00313 expression in TGCT. The migratory and invasive properties of TGCT cells were augmented by LINC00313 , likely via its effects on modulating the expression of epithelial-mesenchyme transition (EMT) related proteins: CTNNB1, ZEB1, CDH2, Snail and VIM. Moreover, LINC00313 expression and CNV correlated negatively with the infiltration of immune cells. In addition, Panobinostat might be a possible candidate drug to target LINC00313 in TGCT. LINC00313 performs important pro-migration and invasion functions in the pathogenesis of TGCT. LINC00313 could be used as diagnostic, prognostic, immune marker and therapeutic target to develop effective treatment of TGCT.

TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma

“…Fifty non-redundant individual miRNAs or miRNA clusters targeting TCF7, 23 miRNAs targeting LINC00313 and 16 common miRNAs for the two transcripts were found. By searching the current literature for established associations between LINC00313 and miRNA, with a special interest on the 16 aforementioned predicted miRNAs, we observed that LINC00313 may induce cell migration and invasion, possibly by inducing β-catenin and EMT by sequestering miR-138-5p, miR-150-5p, miR-204-5p and miR-205-5p, which target the EMT-associated VIM and ZEB1 mRNAs (Liu et al, 2022a ). In addition, TCF7 could be transcriptionally regulated by β-catenin and TCF7L2 transcription factors (Zhu et al, 2015 ).…”

Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data

“…Their up-regulation has been significantly correlated with poor overall survival. This correlation has been attributed to their role in modulating the expression of epithelial–mesenchyme transition (EMT)-related proteins, regulating High Mobility Group AT-Hook 2 (HMGA2), and activating Wnt/β-catenin signaling [ 30 , 31 , 32 ]. We observed that these lncRNAs were significantly up-regulated in FLC samples.…”

Long non-coding RNA TTTY14 promotes cell proliferation and functions as a prognostic biomarker in testicular germ cell tumor

“…Studies have shown that TGCTs are caused by abnormal expression of genes that related to proliferation, pluripotency, and epigenetics. Our previous study found that several long non-coding RNAs (LncRNAs), including lncRNAs RFPL3S, LINC00313, and LINC00467, played important roles in TGCT proliferation, invasion, and functioned as prognostic biomarkers [ [7] , [8] , [9] ]. This indicates that long non-coding RNAs play an important role in the occurrence and development of TGCT.…”