Jia-Xin Chen1, Da Xu1, Jian-Wei Cao1, Li Zuo2, Zhi-Tao Han3, Yi-Jun Tian1, Chuan-Min Chu1, Wang Zhou4, Xiu-Wu Pan5, Xin-Gang Cui6. 1. Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 200433, China, Shanghai. 2. Department of Urology, Changzhou Second People's Hospital, Changzhou, 213000, China. 3. Nanjing University of Traditional Chinese Medicine School of Medical and Life Sciences, Nanjing, 210023, China. 4. Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 200433, China, Shanghai. brilliant212@163.com. 5. Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 200433, China, Shanghai. panxiuwu@smmu.edu.cn. 6. Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 200433, China, Shanghai. cuixingang@smmu.edu.cn.
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.
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 humanrenal 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.
Authors: Robert J Motzer; Thomas E Hutson; Piotr Tomczak; M Dror Michaelson; Ronald M Bukowski; Olivier Rixe; Stéphane Oudard; Sylvie Negrier; Cezary Szczylik; Sindy T Kim; Isan Chen; Paul W Bycott; Charles M Baum; Robert A Figlin Journal: N Engl J Med Date: 2007-01-11 Impact factor: 91.245
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