TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination
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 t...
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doaj-78ea8d203c0f477aa76156d8cc552fe72021-02-23T14:57:09ZengBMCCancer Cell International1475-28672021-02-0121111310.1186/s12935-021-01831-0TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitinationJia-xin Chen0Da Xu1Jian-wei Cao2Li Zuo3Zhi-tao Han4Yi-jun Tian5Chuan-min Chu6Wang Zhou7Xiu-wu Pan8Xin-gang Cui9Department of Urology, Third Affiliated Hospital of the Second Military Medical UniversityDepartment of Urology, Third Affiliated Hospital of the Second Military Medical UniversityDepartment of Urology, Third Affiliated Hospital of the Second Military Medical UniversityDepartment of Urology, Changzhou Second People’s HospitalNanjing University of Traditional Chinese Medicine School of Medical and Life SciencesDepartment of Urology, Third Affiliated Hospital of the Second Military Medical UniversityDepartment of Urology, Third Affiliated Hospital of the Second Military Medical UniversityDepartment of Urology, Third Affiliated Hospital of the Second Military Medical UniversityDepartment of Urology, Third Affiliated Hospital of the Second Military Medical UniversityDepartment of Urology, Third Affiliated Hospital of the Second Military Medical UniversityAbstract 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.https://doi.org/10.1186/s12935-021-01831-0Renal cell carcinomaE3 ubiquitin ligaseProliferationP53TRIM47 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jia-xin Chen Da Xu Jian-wei Cao Li Zuo Zhi-tao Han Yi-jun Tian Chuan-min Chu Wang Zhou Xiu-wu Pan Xin-gang Cui |
spellingShingle |
Jia-xin Chen Da Xu Jian-wei Cao Li Zuo Zhi-tao Han Yi-jun Tian Chuan-min Chu Wang Zhou Xiu-wu Pan Xin-gang Cui TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination Cancer Cell International Renal cell carcinoma E3 ubiquitin ligase Proliferation P53 TRIM47 |
author_facet |
Jia-xin Chen Da Xu Jian-wei Cao Li Zuo Zhi-tao Han Yi-jun Tian Chuan-min Chu Wang Zhou Xiu-wu Pan Xin-gang Cui |
author_sort |
Jia-xin Chen |
title |
TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination |
title_short |
TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination |
title_full |
TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination |
title_fullStr |
TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination |
title_full_unstemmed |
TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination |
title_sort |
trim47 promotes malignant progression of renal cell carcinoma by degrading p53 through ubiquitination |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2021-02-01 |
description |
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. |
topic |
Renal cell carcinoma E3 ubiquitin ligase Proliferation P53 TRIM47 |
url |
https://doi.org/10.1186/s12935-021-01831-0 |
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