Aging
Navigate
Submit an Article
Research Paper|Volume 13, Issue 17|pp 21712—21728

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

Guohai Xie1,2,3, Xinyi Zheng4, Zhong Zheng5, Ruoyu Wu5, Zhixian Yao5, Wenjie Huang5, Feng Sun5, Xingyu Mu5, Ke Wu5, Junhua Zheng2,5
  • 1Department of Urology, Ningbo First Hospital, Ningbo 315000, Zhejiang, China
  • 2Tongji University School of Medicine, Shanghai 20092, Shanghai, China
  • 3Ningbo Clinical Research Center for Urological Disease, Ningbo First Hospital, Ningbo 315010, Zhejiang, China
  • 4Department of Pharmacy, Huashan Hospital, Shanghai 200040, Shanghai, China
  • 5Department of Urology, Shanghai General Hospital, Shanghai 200080, Shanghai, China
* Equal contribution
Received: May 27, 2021Accepted: August 23, 2021Published: September 13, 2021
https://doi.org/10.18632/aging.203514

Copyright: © 2021 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.