<p>LncRNA PVT1 promotes proliferation, invasion and epithelial&ndash;mesenchymal transition of renal cell carcinoma cells through downregulation of miR-16-5p</p>

Abstract

Background LncRNAs have recently emerged as vital regulators in the pathogenesis and development of various cancers. LncRNA PVT1 is reported to function as an oncogene in some tumors. However, the role of PVT1 in RCC remains unknown. Purpose To explore the potential effects of lncPVT1 on the development of renal cell carcinoma. Methods The expression of PVT1 in renal cancer cell lines and tissues was measured by qRT-PCR. The endogenous PVT1 was silenced by RNAi. Cell viabilities were measured by the MTT assay. The migration and invasion of cells were investigated by the transwell assay. The apoptosis of cells was measured by the Nucleosome ELISA and caspase-3 activity assays. The levels of proteins were measured by the western blot. Results We found that PVT1 was upregulated in RCC tissues compared with the adjacent normal tissues. PVT1 expression was closely correlated with TNM stage, Fuhrman grade, lymph node metastasis and tumor size. Kaplan–Meier analysis revealed that high expression of PVT1 was significantly associated with poor overall survival. In accordance, overexpression of PVT1 was observed in RCC cells comto HK-2 cell. Silencing of PVT1 significantly repressed cell viability, induced apoptosis and inhibited cell migration and invasion in vitro. Furthermore, bioinformatic analysis and luciferase reporter assay confirmed that miR-16-5p was a target of PVT1. Silencing of miR-16-5p mostly reversed the regulatory effects on RCC cells induced by downregulation of PVT1. Conclusion In summary, our study indicates that targeting PVT1 might represent a rational therapeutic strategy for RCC.

<p>Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis</p>

“…For example, the amplification of PVT1 promoted ovarian cancer cell proliferation by binding to miR-140; 14 PVT1 promoted cell proliferation, invasion and epithelial-mesenchymal transition (EMT) in renal cell carcinoma via mediating the down-regulation of miR-16-5p. 15 MiR-106b-5p, a member of miR-106b ~ 25 clusters, has also been identified to be up-regulated in CRC tissues and implicate in the invasion and metastasis of CRC cells. 16,17 Four jointed box 1 (FJX1) is a notchinducible secreted ligand, which is homologous to the Drosophila four-jointed (fj) gene.…”

PVT1 Promotes Cancer Progression via MicroRNAs

“…Bcl-2 is a key factor that alters the permeability of the mitochondrial outer membrane and allows tumor cells to escape apoptosis. With PVT1 overexpression, miR-16-5p (26) or miR-195 (27) are inhibited, and thus their downstream gene Bcl-2 is overexpressed. PVT1 also plays a role in regulating the apoptosis of tumor cells through activating c-MET/PI3K/AKT and co-activator-associated arginine methyltransferase 1 (CARM1) signaling pathways by sponging miR-152 and miR-424-5p, respectively (5, 28) (Figure 1).…”

“…PVT1 regulates plasminogen activator inhibitor 1 RNA-binding protein (SERBP1), plasminogen activator inhibitor-1 (PAI-1), and other molecules by competitively binding to miR-448, thereby reducing the expression of E-cadherin and promoting the invasion of cancer cells (34–36). In addition, E-cadherin can also be down-regulated directly by PVT1 through regulation of miR-16-5p (26, 37) (Figure 2).…”

<p>LncRNA PVT1 Enhances Proliferation and Cisplatin Resistance via Regulating miR-194-5p/HIF1a Axis in Oral Squamous Cell Carcinoma</p>

“…9 Silence of PVT1 was reported to significantly inhibit proliferation, invasion and epithelial-mesenchymal transition via reducing miR-16-5p in renal cell carcinoma cells. 10 In ovarian cancer, PVT1 up-regulated SOX2 expression to promote cell proliferation and invasion. 11 These findings support a crucial clinical value for PVT1 in the development of useful biomarker and targeted therapy.…”