TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination

Author:

Chen Jia-xin,Xu Da,Cao Jian-wei,Zuo Li,Han Zhi-tao,Tian Yi-jun,Chu Chuan-min,Zhou Wang,Pan Xiu-wu,Cui Xin-gangORCID

Abstract

Abstract Background Renal cell carcinoma (RCC) is one of the most common malignant tumors originating from the renal parenchymal urinary epithelial system. Tripartite motif 47 (TRIM47) is a member of the TRIM family proteins, which has E3 ligase activity and has been demonstrated to be involved in the occurrence and prognosis of many tumors. The main purpose of this study is to explore the role and potential mechanism of TRIM47 in promoting malignant biological behavior of RCC. Materials and methods TRIM47 mRNA and protein levels in human renal cancer and paired normal adjacent tissues were detected by qRT-PCR and Western blot. The effects of TRIM47 knockdown and overexpression in renal cell carcinoma cells on cell proliferation, invasion and xenograft tumor growth in nude mice were analyzed. The molecular mechanism was explored by mass spectrometric exploration,Western blot and immunoprecipitation assays. Results TRIM47 promoted RCC cell proliferation in vitro and in vivo as an oncogene. Mechanistically, TRIM47 exerted an E3 ligase activity by interacting with P53 protein to increase its ubiquitination and degradation, which further promoted the malignant biological behavior of RCC. Conclusions Our study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.

Funder

National Natural Science Foundation of China

National Natural Science Foundation of China for Youth

Program of Shanghai Academic/Technology Research Leader

Shanghai Sailing Program

The Top-level Clinical Discipline Project of Shanghai Pudong

Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project

Technology Project of Jiading District Health System

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics,Oncology

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