TRIM65 Promotes Cervical Cancer Through Selectively Degrading p53-Mediated Inhibition of Autophagy and Apoptosis
Xiaoyu Wang, Hai-Wei Mao, Xiao‐Hui Guan, Qiming Huang, Zhenping Yu, Jie Wu, Hui-Lan Tan, Feng Zhang, Xuan Huang, Ke‐Yu Deng, Hongbo Xin
Abstract
Tripartite motif containing 65 (TRIM65) is an E3 ubiquitin ligase that has been implicated in a variety of cellular processes as well as tumor progression, but its biological role and the underlying mechanism in cervical cancer is unclear. Here, we reported that TRIM65 expression in human cervical cancer tissues was significantly higher than that in the adjacent normal cervical tissues, and TRIM65 knockdown enhanced autophagic flux and cell apoptosis, but not cell cycle, to dramatically inhibit the proliferation and migration of cervical cancer cells. Furthermore, our experiments showed that TRIM65 exhibited oncogenic activities via directly targeting p53, a tumor suppressor and a common upsteam regulator between autophagy and apoptosis, promoting ubiquitination and proteasomal degradation of p53. Taken together, our studies demonstrated that TRIM65 knockdown promotes cervical cancer cell death through enhancing autophagy and apoptosis, suggesting that TRIM65 may be a potential therapeutic target for cervical cancer clinically.