UBAP2 negatively regulates the invasion of hepatocellular carcinoma cell by ubiquitinating and degradating Annexin A2

// Dou-Sheng Bai 1, 2, * , Chao Wu 1, 2, * , Liu-Xiao Yang 2, * , Chi Zhang 2, * , Peng-Fei Zhang 2, * , Yi-Zhou He 2, * , Jia-Bin Cai 2 , Zheng-Ji Song 3 , Zhao-Ru Dong 2 , Xiao-Yong Huang 2 , Ai-Wu Ke 2 , Guo-Ming Shi 2 1 Department of Hepatobiliary and Pancreatic Surgery, Clinical Medical College of Yangzhou University, Jiangsu, 225001, P.R. China 2 Liver Cancer Institute and Department of Liver Surgery of Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, 200032, P.R. China 3 Department of Digestion, The First People’s Hospital of Yunnan Province, Yunnan, 650000, P.R. China * These authors contributed equally to this work Correspondence to: Guo-Ming Shi, email: shi.guoming@zs-hospital.sh.cn Ai-Wu Ke, email: ke.aiwu@zs-hospital.sh.cn Keywords: hepatocellular carcinoma, ubiquitin associated protein 2, Annexin A2, ubiquitination, invasion Received: September 17, 2015      Accepted: March 28, 2016      Published: April 18, 2016 ABSTRACT The ubiquitin-dependent proteasomal degradation of proteins controls signaling and cellular survival. In this study, we found that ubiquitin associated protein 2 (UBAP2) was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent normal tissues. Furthermore, higher expression of UBAP2 in cancer tissues was correlated with good prognosis in HCC patients. Knockdown of UBAP2 significantly enhanced the invasion and proliferation of HCC cells in vitro and promoted tumor growth in vivo , while enforced expression of UBAP2 impaired the aggressive ability and tumor growth of HCC cells. Mechanistically, UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination, and then inhibited HCC progression. Collectively, UBAP2 appears as a novel marker for predicting prognosis and a therapeutic target for HCC.