The E3 ubiquitin ligase TRIM17 promotes gastric cancer survival and progression via controlling BAX stability and antagonizing apoptosis

E3泛素连接酶TRIM17通过控制BAX稳定性和拮抗细胞凋亡促进胃癌存活和进展

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作者:Jiajia Shen #, Hang Yang #, Xinran Qiao, Yang Chen, Liyun Zheng, Jingyu Lin, Jingyu Lang, Qiang Yu, Zhen Wang

Abstract

Tripartite motif 17 (TRIM17) belongs to a subfamily of the RING-type E3 ubiquitin ligases, and regulates several cellular processes and pathological conditions including cancer. However, its potential function in gastric cancer (GC) remains obscure. Here, we have found TRIM17 mRNA and protein levels are both upregulated in human GC compared with normal specimens, and TRIM17 upregulation indicates poor survival for GC patients. Functionally, TRIM17 was found to act as an oncogene by promoting the proliferation and survival of GC cell lines AGS and HGC-27. Mechanistically, TRIM17 acts to interact with BAX and promote its ubiquitination and proteasomal degradation, leading to a deficiency in BAX-dependent apoptosis in GC cells in the absence and presence of apoptosis stimuli. Moreover, TRIM17 and BAX expression levels are inversely correlated in human GC specimens. Our data thus suggest TRIM17 contributes to gastric cancer survival through regulating BAX protein stability and antagonizing apoptosis, which provides a promising therapeutic target for GC treatment and a biomarker for prognosis.

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