Objective: Long noncoding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is aberrantly expressed and involved in the promotion of various cancers. However, the vital epigenetic function of PVT1-214, a transcript isoform of PVT1, in gastric cancer (GC) remains unknown. We aimed to investigate the dysregulation and detailed mechanism underlying the involvement of lncRNA PVT1-214 in GC.
Patients and methods: The expression of PVT1-214 in GC tissues and cell lines was detected by qRT-PCR. The relationship between increased PVT1-214 levels and the advanced clinicopathological features of tumor tissues was analyzed using a Chi-square test. The influence of PVT1-214 on the survival rate of GC cell lines was evaluated by the log-rank test. Cell lines were used to explore the carcinogenic effects of PVT1-214 in vitro and in vivo, and specific tests included cell apoptosis determined by flow cytometry, cell proliferation assayed by Cell Counting Kit-8 (CCK-8) and colony formation, and the use of these cells for mice xenograft models. Direct complementary binding was predicted by bioinformatics and verified by dual luciferase reporter assay, RNA transfection, quantitative polymerase chain reaction (qPCR), and Western blotting. Spearman's correlation coefficient was adopted to evaluate the correlation between miR-128 and PVT1-214 levels.
Results: PVT1-214 expression in GC tissues and cell lines is markedly elevated. In GC patients, high expression of PVT1-214 is associated with late tumor stage, increased tumor size, and poor survival. PVT1-214 silencing represses cell proliferation and enhances apoptosis of GC cells both in vivo and in vitro. Additionally, PVT1-214 functions as a competing endogenous RNA (ceRNA) by binding to miR-128. Inhibition of miR-128 releases Tropomyosin receptor kinase C (TrkC) from the complementary binding complex, subsequently increasing the protein level of TrkC in GC cells.
Conclusions: PVT1-214-induced miR-128 repression regulates TrkC to further the progression of GC, indicating that this process will provide a promising therapeutic target in GC.