Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer

Liu,Li; Yao,Dan; Zhang,Pengbo; Ding,Weichao; Zhang,Xiuzhong; Zhang,Chong; Gong,Shuai; Zhang,Yi; Wang,Jike; Sun,Ting; Ren,Zeqiang

doi:10.3892/or.2017.6050

Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer

Authors:
- Li Liu
- Dan Yao
- Pengbo Zhang
- Weichao Ding
- Xiuzhong Zhang
- Chong Zhang
- Shuai Gong
- Yi Zhang
- Jike Wang
- Ting Sun
- Zeqiang Ren
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Affiliations: Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China, Department of Gastrointestinal Surgery, Huai'an Second People's Hospital, Huaian, Jiangsu 223000, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/or.2017.6050
Pages: 3531-3537

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Abstract

Ubiquitin specific peptidase 9, X-linked (USP9X), a significant regulatory protease in protein ubiquitination, has been proven to act as a proto-oncogene in several types of cancers, such as cervix, colon, breast, brain and lung cancers. The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to its high invasive and metastatic abilities. Nevertheless, whether USP9X acts as a proto-oncogene or a tumor-suppressor gene in PDAC is controversial and the mechanism of metastasis remains unknown. The present study focused on the effect of USP9X on the migration, invasion and apoptosis of PADC cells. We analyzed the expression of USP9X in pancreatic cancer tissues of different pathologic grades by immunohistochemical analysis. USP9X expression in the pancreatic cancer tissues was markedly increased in contrast to that noted in the adjacent non-tumor tissues. USP9X expression in PANC-1 cells was downregulated after transfection of shRNA-USP9X. Knockdown of endogenous USP9X expression evidently inhibited the migration and invasion of PANC-1 cells, and promoted cell apoptosis. Meanwhile, expression levels of Snail, Twist, N-cadherin and vimentin were downregulated. E-cadherin expression was negatively correlated with USP9X expression and the expression of survivin was also downregulated in the PANC-1 cells. In brief, USP9X promoted the migration and invasion of PANC-1 cells probably by provoking epithelial-mesenchymal transition, and also inhibited apoptosis. We believe that USP9X is a major oncogene that may play a significant role in the treatment and prognosis of PDAC.

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