Knockdown of ubiquitin-like modifier-activating enzyme 2 promotes apoptosis of clear cell renal cell carcinoma cells.
Knockdown of ubiquitin-like modifier-activating enzyme 2 promotes apoptosis of clear cell renal cell carcinoma cells.
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泛素样修饰激活酶2的敲低促进透明细胞肾细胞癌细胞凋亡
DOI：
10.1038/s41419-021-04347-7
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发表时间：
2021-11-09
影响因子：
9
通讯作者：
Zou X
中科院分区：
文献类型：
--
作者：
Zhang G;Zou J;Shi J;Qian B;Qiu K;Liu Q;Xie T;He Z;Xu H;Liao Y;Wu Y;Li Y;Xiao G;Yuan Y;Xiao R;Wu G;Zou X
小泛素相关修饰物（SUMO）蛋白参与肿瘤的发展。泛素样修饰激活酶2（UBA 2）是SUMO修饰系统的重要成员;然而，其在肾透明细胞癌（ccRCC）中的作用尚不清楚。因此，我们研究了UBA 2在ccRCC中的表达和功能。UBA 2的mRNA和蛋白表达水平在ccRCC中均高于正常肾组织，且与肿瘤大小、Fuhrman分级和肿瘤分期显著相关。UBA 2敲低抑制ccRCC细胞生长，促进体外和体内细胞凋亡，并降低p53突变体c-Myc和SUMO修饰系统关键酶的丰度。而UBA 2的过表达则具有相反的作用。p53突变体或c-Myc的过表达减轻了UBA 2敲低对ccRCC细胞增殖和凋亡的影响。总之，靶向UBA 2可能对ccRCC具有治疗潜力。
Small ubiquitin-related modifier (SUMO) proteins are involved in the development of tumors. Ubiquitin-like modifier-activating enzyme 2 (UBA2) is an important member of the SUMO modification system; however, its role in clear cell renal cell carcinoma (ccRCC) is unclear. Therefore, we investigated the expression and function of UBA2 in ccRCC. Both mRNA and protein expression levels of UBA2 were found to be higher in ccRCC than in normal renal tissues and significantly related to the tumor size, Fuhrman grade, and tumor stage. UBA2 knockdown inhibited ccRCC cell growth, promoted apoptosis in vitro and in vivo, and decreased the abundance of a p53 mutant, c-Myc, and key enzymes of the SUMO modification system. Meanwhile, overexpression of UBA2 had the opposite effects. Overexpression of the p53 mutant or c-Myc alleviated the effects of UBA2 knockdown on ccRCC cell proliferation and apoptosis. In conclusion, targeting UBA2 may have a therapeutic potential against ccRCC.
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