Open AccessZHX3 promotes the progression of urothelial carcinoma of the bladder via repressing of RGS2 and is a novel substrate of TRIM21
Author(s) -
Deng Minhua,
Wei Wensu,
Duan Jinling,
Chen Rixin,
Wang Ning,
He Leye,
Peng Yulu,
Ma Xiaodan,
Wu Zeshen,
Liu Jianye,
Li Zhiyong,
Zhang Zhiling,
Jiang Lijuan,
Zhou Fangjian,
Xie Dan
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14810
Subject(s) - rgs2 , cancer research , regulator of g protein signaling , metastasis , immunoprecipitation , pathogenesis , bladder cancer , homeobox , medicine , downregulation and upregulation , biology , cancer , gene , transcription factor , genetics , gtpase activating protein , receptor , g protein
Clinically, patients with urothelial carcinoma of the bladder (UCB) with tumor metastasis are incurable. To find new therapeutic strategies, the mechanisms underlying UCB invasion and metastasis should be further investigated. In this study, zinc finger and homeobox 3 (ZHX3) was first screened as a critical oncogenic factor associated with poor prognosis in a UCB dataset from The Cancer Genome Atlas (TCGA). These results were also confirmed in a large cohort of clinical UCB clinical samples. Next, we found that ZHX3 could promote the migration and invasion capacities of UCB cells both in vitro and in vivo. Mechanistically, coimmunoprecipitation (coIP) and mass spectrometry (MS) analysis indicated that ZHX3 was a target of tripartite motif 21 (TRIM21), which mediates its ubiquitination, and subsequent degradation. Notably, RNA‐seq analysis showed that ZHX3 repressed the expression of regulator of G protein signaling 2 (RGS2). Generally, our results suggest that ZHX3 plays an oncogenic role in UCB pathogenesis and might serve as a novel therapeutic target for UCB.