Ubiquitin specific protease 22 promotes cell proliferation and tumor growth of epithelial ovarian cancer through synergy with transforming growth factor β1

泛素特异性蛋白酶22与转化生长因子β1协同促进上皮性卵巢癌细胞增殖和肿瘤生长

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作者:Mei Ji, Huirong Shi, Ya Xie, Zhao Zhao, Shunshuang Li, Cheng Chang, Xinghan Cheng, Yue Li

Abstract

Ubiquitin specific protease 22 (USP22) is an oncogene that is upregulated in many cancer types, and aberrant expression of USP22 correlates with clinical outcome. However, its potential functional impact in epithelial ovarian cancer (EOC) has not been determined. Here, we report that USP22 was upregulated in EOC specimens and EOC cell lines with important functional consequences. A high level of USP22 in EOC tissues was associated with advanced clinical FIGO stage, lymph node metastasis and worse prognosis. Patients with higher USP22 expression had shorter relapse-free and overall survival. Depletion of USP22 suppressed cell proliferation in vitro and tumor growth in vivo. We found that inhibition of USP22 suppressed cell proliferation by inducing G1 phase cell cycle arrest through synergy with oncogenic transforming growth factor-β1 (TGFB1). Our results indicate that USP22 functions as an oncogene in EOC, and thus USP22 may serve as a potential therapeutic target for individualized EOC treatment.

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