The ceRNA PVT1 inhibits proliferation of ccRCC cells by sponging miR-328-3p to elevate FAM193B expression.

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common and fatal malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers, warranting the detailed investigation of their biological functions and molecular mechanisms. In this study, we explored the role and mechanism of plasmacytoma variant translocation 1 (PVT1), a competitive endogenous RNA (ceRNA) in ccRCC tissues in vitro and in vivo. We found that PVT1 is upregulated in ccRCC cells and promoted cell proliferation. Bioinformatic analysis, dual-luciferase reporter assays, argonaute 2-RNA immunoprecipitation (AGO2-RIP), quantitative PCR arrays, western blot assay, and rescue experiments were conducted to explore the underlying mechanisms of PVT1. Our analyses revealed that miR-328-3p was a direct target of PVT1 and that FAM193B was a direct target of miR-328-3p. FAM193B is upregulated in ccRCC tissues and promotes cell proliferation by activating the MAPK/ERK and PI3K/AKT pathways. Our results indicated that PVT1 promotes ccRCC cells proliferation by sponging miR-328-3p to upregulate FAM193B and activate the MAPK/ERK and PI3K/AKT pathways. Collectively, these results suggest that PVT1- miR-328-3p-FAM193B loop could serve as a potential biomarker and therapeutic target for ccRCC.

• Authors: Guohai Xie, Xinyi Zheng, Zhong Zheng, Ruoyu Wu, Zhixian Yao, Wenjie Huang, Feng Sun, Xingyu Mu, Ke Wu, Junhua Zheng
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 17 Pg. 21712-21728 (09 13 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 34518442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FAM193B protein, human
• MIRN328 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• PVT1 long-non-coding RNA, human
• RNA, Long Noncoding
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Carcinoma, Renal Cell (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kidney Neoplasms (genetics)
• Male
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Neoplasm Proteins (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• RNA, Long Noncoding (genetics)
• Signal Transduction (genetics)
• Xenograft Model Antitumor Assays