UBAP2 negatively regulates the invasion of hepatocellular carcinoma cell by ubiquitinating and degradating Annexin A2.
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.
Department of Hepatobiliary and Pancreatic Surgery, Clinical Medical College of Yangzhou University, Jiangsu, 225001, P.R. China.|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.
Dou-Sheng
DS
Bai
Department of Hepatobiliary and Pancreatic Surgery, Clinical Medical College of Yangzhou University, Jiangsu, 225001, P.R. China.|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.
Chao
C
Wu
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.
Liu-Xiao
LX
Yang
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.
Chi
C
Zhang
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.
Peng-Fei
PF
Zhang
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.
Yi-Zhou
YZ
He
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.
Jia-Bin
JB
Cai
Department of Digestion, The First People's Hospital of Yunnan Province, Yunnan, 650000, P.R. China.
Zheng-Ji
ZJ
Song
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.
Zhao-Ru
ZR
Dong
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.
Xiao-Yong
XY
Huang
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.
Ai-Wu
AW
Ke
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.
Guo-Ming
GM
Shi
D017306:Annexin A2 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D054875:Ubiquitination
C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C000595671:Ubap2L protein, human
Annexin A2; hepatocellular carcinoma; invasion; ubiquitin associated protein 2; ubiquitination