LncRNA PVT1 Promotes Cell Proliferation, Invasion, and Migration and Inhibits Cell Apoptosis by Phosphorylating YAP

Abstract

Gastric cancer (GC) as a serious global health problem is a threat to human longevity. Plasmacytoma variant translocation 1 (PVT1) participates in the formation and progression of various cancers, including GC. The aim of this study is to investigate the mechanism underlying the functions of PVT1 and explore a novel target for the diagnosis and treatment of GC. Analysis of the TCGA dataset using the R software identified that the lncRNA PVT1 was greatly upregulated in GC tissues. Twenty pairs of GC and adjacent normal tissues were acquired from patients with GC, and the expression of PVT1 was evaluated using RT-qPCR. Furthermore, PVT1 expression was knocked down in GC cells using siRNA, and the GC cells were divided into control, negative control (NC), and siRNA groups. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) and colony formation assays, whereas cell migration and invasion ability were investigated through wound healing and Transwell assays. Moreover, Western blotting was used to analyze the expression of Yes-associated protein (YAP) and epithelial-to-mesenchymal transition (EMT) proteins. We also found that PVT1 and YAP expressions were upregulated in the GC tissues compared with those in the adjacent nontumor tissues. Knockdown of PVT1 was found to inhibit the proliferation, invasion, and migration and promote apoptosis of GC cells. Furthermore, knockdown of PVT1 downregulated YAP and promoted phosphorylation of YAP, suggesting that PVT1 exerts actions on GC cells by targeting YAP and inhibits cell apoptosis in vitro. The EMT process was also inhibited by the knockdown of PVT1. In summary, lncRNA PVT1 facilitated cell proliferation, invasion, and migration and suppressed cell apoptosis by targeting YAP. This study suggests that the expressions of PVT1 and YAP could be used for the early detection of GC and the occurrence and development of GC could be inhibited by interfering the interaction of PVT1 and YAP, which will provide new insights for the diagnosis, treatment, and prognosis of GC.

Constructing a personalized prognostic risk model for colorectal cancer using machine learning and multi‐omics approach based on epithelial–mesenchymal transition‐related genes

“…Our analysis demonstrated significant negative correlations between PVT1 and two of the identified core genes, suggesting a possible inhibitory role of PVT1 in their regulation. lncRNA PVT1 has been implicated in the regulation of EMT and cancer progression in various cancers, including CRC 39–41 . Our findings add to the growing body of evidence supporting the functional relevance of PVT1 in EMT regulation and provide a basis for further investigations into the molecular mechanisms and therapeutic potential of targeting PVT1 in CRC.…”

“…lncRNA PVT1 has been implicated in the regulation of EMT and cancer progression in various cancers, including CRC. [39][40][41] Our findings add to the growing body of evidence supporting the functional relevance of PVT1 in EMT regulation and provide a basis for further investigations into the molecular mechanisms and therapeutic potential of targeting PVT1 in CRC.…”