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

Cancer Cell International

Li Zuo¹  Chuan-min Chu²  Xin-gang Cui²  Jia-xin Chen²  Xiu-wu Pan²  Da Xu²  Jian-wei Cao²  Wang Zhou²  Yi-jun Tian²  Zhi-tao Han³ 

[1] Department of Urology, Changzhou Second People’s Hospital, 213000, Changzhou, China;Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 200433, Shanghai, China;Nanjing University of Traditional Chinese Medicine School of Medical and Life Sciences, 210023, Nanjing, China;

关键词: Renal cell carcinoma;    E3 ubiquitin ligase;    Proliferation;    P53;    TRIM47;   

DOI  :  10.1186/s12935-021-01831-0

来源: Springer

【 摘 要 】

BackgroundRenal 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 methodsTRIM47 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.ResultsTRIM47 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.ConclusionsOur study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.

【 授权许可】

CC BY