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

癌症研究 泛素连接酶 基因敲除 免疫印迹 细胞生长 泛素 癌变 癌基因 肾细胞癌 细胞 医学 癌症 生物 细胞培养 化学 病理 细胞周期 内科学 基因 生物化学 遗传学
作者
Jiaxin Chen,Da Xu,Jun Cao,Li Zuo,Zhitao Han,Yijun Tian,Chuanmin Chu,Zhou Wang,Xiuwu Pan,Xingang Cui
出处
期刊:Cancer Cell International [BioMed Central]
卷期号:21 (1) 被引量:14
标识
DOI:10.1186/s12935-021-01831-0
摘要

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.
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