Research Papers:

USP22 maintains gastric cancer stem cell stemness and promotes gastric cancer progression by stabilizing BMI1 protein

Yue Ma, Hua-Lin Fu, Zhen Wang, Hai Huang, Jian Ni, Jie Song, Ying Xia, Wei-Lin Jin _ and Da-Xiang Cui

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Oncotarget. 2017; 8:33329-33342. https://doi.org/10.18632/oncotarget.16445

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Yue Ma1,2, Hua-Lin Fu1,3, Zhen Wang4, Hai Huang5, Jian Ni1,3, Jie Song1,3, Ying Xia5, Wei-Lin Jin1,3 and Da-Xiang Cui1,2,3

1Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

2School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

3National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai 200240, China

4Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi’an Jiao Tong University, Xi’an 710049, China

5Department of Clinical Biochemistry, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou 550005, China

Correspondence to:

Wei-Lin Jin, email: weilinjin@sjtu.edu.cn

Da-Xiang Cui, email: dxcui@sjtu.edu.cn

Keywords: USP22, BMI1, gastric cancer stem cell, gastric cancer, deubiquitinase

Received: December 15, 2016    Accepted: March 09, 2017    Published: March 22, 2017


Increased ubiquitin-specific protease 22 (USP22) has been associated with poor prognosis in several cancers including gastric cancer. However, the role of USP22 in gastric tumorigenesis is still unclear. Gastric cancer stem cells have been identified and shown to correlate with gastric cancer initiation and metastasis. In this study, we found that silencing of USP22 inhibited proliferation of gastric cancer cells and suppressed the cancer stem cell spheroid formation in serum-free culture. Furthermore, cancer stem cell markers, such as CD133, SOX2, OCT4 and NANOG were down-regulated. Additionally, knockdown of USP22 inhibited gastric cancer xenografts growth. Our analysis of TCGA database indicated that BMI1 overexpression may predict gastric cancer patient survival, and TAT-BMI1 proteins reversed the USP22 knockdown-mediated decreased in cancer stem cell properties, and elevated the expression of stemness-associated genes. Furthermore, we found that overexpression of USP22 stabilized the BMI1 protein in gastric cancer cells. Taken together, our study demonstrates that USP22 is indispensable for gastric cancer stem cell self-renewal through stabilization of BMI1. These results may provide novel approaches to the theranostics of gastric cancer in the near future.

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