Hepatitis B virus X upregulates HuR protein level to stabilize HER2 expression in hepatocellular carcinoma cells.
Hepatitis B virus- (HBV-) associated hepatocellular carcinoma (HCC) is the most common type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very complicated and HBV-encoded X protein (HBx) has been reported to play the most important role in this process. Activation of downstream signal pathways of epidermal growth factor receptor (EGFR) family is known to mediate HBx-dependent HCC tumor progression. Interestingly, HER2 (also known as ErbB2/Neu/EGFR2) is frequently overexpressed in HBx-expressing HCC patients and is associated with their poor prognosis. However, it remains unclear whether and how HBx regulates HER2 expression. In this study, our data showed that HBx expression increased HER2 protein level via enhancing its mRNA stability. The induction of RNA-binding protein HuR expression by HBx mediated the HER2 mRNA stabilization. Finally, the upregulated HER2 expression promoted the migration ability of HBx-expressing HCC cells. These findings deciphered the molecular mechanism of HBx-mediated HER2 upregulation in HBV-associated HCC.
Department of General Surgery, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan ; School of Medicine for International Students, I-Shou University, Kaohsiung 824, Taiwan.
Chao-Ming
CM
Hung
Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan ; Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan ; The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan ; Department of Biotechnology, Asia University, Taichung 413, Taiwan.
Wei-Chien
0000-0001-6467-8716
WC
Huang
Department of Medical Research, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan.
Hsiao-Lin
HL
Pan
Department of Medical Research, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan.
Pei-Hsuan
PH
Chien
Department of Medicine and Department of Health Examination, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan ; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Chih-Wen
CW
Lin
Department of Nutrition, I-Shou University, Kaohsiung 824, Taiwan.
Lei-Chin
LC
Chen
Department of Biological Science & Technology, I-Shou University, No. 8 Yida Road, Kaohsiung 824, Taiwan.
Yu-Fong
YF
Chien
Department of Biological Science & Technology, I-Shou University, No. 8 Yida Road, Kaohsiung 824, Taiwan.
Ching-Chiao
CC
Lin
Department of Biological Science & Technology, I-Shou University, No. 8 Yida Road, Kaohsiung 824, Taiwan.
Kar-Hee
KH
Leow
Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan.
Wen-Shu
WS
Chen
Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan ; The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan.
Jhen-Yu
JY
Chen
Department of Family Medicine, China Medical University Hospital, Taichung 404, Taiwan.
Chien-Yi
CY
Ho
Department of Medical Research, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan.
Pao-Sheng
PS
Hou
Department of Medical Research, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan ; Department of Biological Science & Technology, I-Shou University, No. 8 Yida Road, Kaohsiung 824, Taiwan.
Yun-Ju
YJ
Chen
D051959:ELAV Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins
D051959:ELAV Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C508053:ERBB2 protein, human