Research Papers:

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

Dou-Sheng Bai, Chao Wu, Liu-Xiao Yang, Chi Zhang, Peng-Fei Zhang, Yi-Zhou He, Jia-Bin Cai, Zheng-Ji Song, Zhao-Ru Dong, Xiao-Yong Huang, Ai-Wu Ke and Guo-Ming Shi _

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Oncotarget. 2016; 7:32946-32955. https://doi.org/10.18632/oncotarget.8783

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Dou-Sheng Bai1,2,*, Chao Wu1,2,*, Liu-Xiao Yang2,*, Chi Zhang2,*, Peng-Fei Zhang2,*, Yi-Zhou He2,*, Jia-Bin Cai2, Zheng-Ji Song3, Zhao-Ru Dong2, Xiao-Yong Huang2, Ai-Wu Ke2, Guo-Ming Shi2

1Department of Hepatobiliary and Pancreatic Surgery, Clinical Medical College of Yangzhou University, Jiangsu, 225001, P.R. China

2Liver 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

3Department 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: [email protected]

Ai-Wu Ke, email: [email protected]

Keywords: hepatocellular carcinoma, ubiquitin associated protein 2, Annexin A2, ubiquitination, invasion

Received: September 17, 2015     Accepted: March 28, 2016     Published: April 18, 2016


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.

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