Usp5 functions as an oncogene for stimulating tumorigenesis in hepatocellular carcinoma

// Yi Liu 1 , Wei-Mao Wang 2 , Ying-Fei Lu 3 , Lu Feng 3 , Li Li 1 , Ming-Zhu Pan 1 , Yu Sun 4 , Chun-Wai Suen 2 , Wei Guo 5 , Jian-Xin Pang 6 , Jin-Fang Zhang 2, 3, 7 and Wei-Ming Fu 6, 7 1 Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, China 2 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China 3 Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China 4 Shenzhen Enhance Techology Co. Ltd., Shenzhen, Guangdong, China 5 Shenzhen Ritzcon Biological Techology Co. Ltd., Shenzhen, Guangdong, China 6 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China 7 Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou, Guangdong, China Correspondence to: Wei-Ming Fu, email: fuweiming76@smu.edu.cn Jian-Xin Pang, email: pjx@smu.edu.cn Keywords: Usp5, epatocellular carcinoma, proliferation, migration, P14 Received: September 06, 2016 Accepted: March 28, 2017 Published: April 06, 2017 ABSTRACT As deubiquitinases, several ubiquitin specific protease members have been reported to mediate tumorigenesis. Although ubiquitin specific protease 5 (Usp5) was previously demonstrated to suppress p53 transcriptional activity and DNA repair, its role in carcinogenesis remains elusive. In this study, we sought to define a novel role of Usp5 in tumorigenesis. It was found that Usp5 was significantly upregulated in hepatocellular carcinoma (HCC) cells and most clinical specimens. Further functional investigation also showed that Usp5 knockdown suppressed cell proliferation, migration, drug resistance and induced apoptosis; on the other hand, Usp5 overexpression promoted colony formation, migration, drug resistance and tumorigenesis. Additionally, the inactivated p14 ARF -p53 signaling was observed in Usp5 overexpressed HCC cells, while this signaling was activated by Usp5 knockdown. Therefore, our data demonstrated that Usp5 contributed to hepatocarcinogenesis by acting as an oncogene, which provides new insights into the pathogenesis of HCC and explores a promising molecular target for HCC diagnosis and therapy.