TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination.
TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination.
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DOI：
10.1186/s12935-021-01831-0
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发表时间：
2021-02-23
影响因子：
5.8
通讯作者：
Cui XG
中科院分区：
文献类型：
--
作者：
Chen JX;Xu D;Cao JW;Zuo L;Han ZT;Tian YJ;Chu CM;Zhou W;Pan XW;Cui XG
肾细胞癌是最常见的起源于肾实质尿路上皮系统的恶性肿瘤之一。Triartite Motif 47(TRIM47)是TRIM家族蛋白中的一员，具有E3连接酶活性，已被证明与许多肿瘤的发生和预后有关。本研究的主要目的是探讨TRIM47在促进肾细胞癌恶性生物学行为中的作用及其可能机制。采用定量逆转录聚合酶链式反应(qRT-PCR)和免疫印迹法检测人肾癌及癌旁正常组织中TRIM47mRNA和蛋白的表达水平。分析TRIM47基因敲除和过表达对肾癌细胞增殖、侵袭和裸鼠移植瘤生长的影响。通过质谱学、免疫印迹和免疫沉淀等方法对其分子机制进行了初步探讨。TRIM47作为一种癌基因在体内外均可促进肾癌细胞的增殖。机制上，TRIM47通过与P53蛋白相互作用，发挥E3连接酶的活性，增加其泛素化和降解，从而进一步促进肾细胞癌的恶性生物学行为。我们的研究表明，TRIM47-P53轴在肾癌的进展中发挥了功能作用，并提示了肾癌潜在的治疗靶点。
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. 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. 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. 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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影响因子：
--
作者：
Chen Y;Guo Y;Yang H;Shi G;Xu G;Shi J;Yin N;Chen D
通讯作者：
Chen D
影响因子：
16.6
作者：
Bailey ST;Smith AM;Kardos J;Wobker SE;Wilson HL;Krishnan B;Saito R;Lee HJ;Zhang J;Eaton SC;Williams LA;Manocha U;Peters DJ;Pan X;Carroll TJ;Felsher DW;Walter V;Zhang Q;Parker JS;Yeh JJ;Moffitt RA;Leung JY;Kim WY
通讯作者：
Kim WY
影响因子：
6.6
作者：
Joo, Hae Mi;Kim, Ji Young;Jin, Young Woo
通讯作者：
Jin, Young Woo
影响因子：
8
作者：
He, GG;Siddik, ZH;Kuang, J
通讯作者：
Kuang, J
影响因子：
--
作者：
Caratozzolo MF;Valletti A;Gigante M;Aiello I;Mastropasqua F;Marzano F;Ditonno P;Carrieri G;Simonnet H;D'Erchia AM;Ranieri E;Pesole G;Sbisà E;Tullo A
通讯作者：
Tullo A