Cell Death and Disease (Nov 2021)

Knockdown of ubiquitin-like modifier-activating enzyme 2 promotes apoptosis of clear cell renal cell carcinoma cells

  • Guoxi Zhang,
  • Junrong Zou,
  • Jinglin Shi,
  • Biao Qian,
  • Kaiyang Qiu,
  • Quanliang Liu,
  • Tianpeng Xie,
  • Zhihua He,
  • Hui Xu,
  • Yunfeng Liao,
  • Yuting Wu,
  • Yanmin Li,
  • Guancheng Xiao,
  • Yuanhu Yuan,
  • Rihai Xiao,
  • Gengqing Wu,
  • Xiaofeng Zou

DOI
https://doi.org/10.1038/s41419-021-04347-7
Journal volume & issue
Vol. 12, no. 11
pp. 1 – 10

Abstract

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Abstract 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.