Hepatitis C virus core protein regulates NANOG expression via the stat3 pathway.
HCV Core plays a role in the development of hepatocellular carcinoma. Aberrant expression of NANOG has been observed in many types of human malignancies. However, relationship between Core and NANOG has not been clarified. In this study, we found that Core is capable of up-regulating NANOG expression. Core-induced NANOG expression was accompanied by enforced expression of phosphorylated stat3 protein and was attenuated by inhibition of stat3 phosphorylation. ChIP showed that phosphorylated stat3 directly binds to the NANOG promoter. Core-induced NANOG expression resulted in enhanced cell growth and cell cycle progression. Knockdown of NANOG blocked the cell cycle at the G0/G1 phases and inhibited the cyclin D1 expression. Our findings provide a new insight into the mechanism of hepatocarcinogenesis by HCV infection.
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China. Electronic address: jiajiazh2004@126.com.
Jia-Jia
JJ
Zhou
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Ru-Fu
RF
Chen
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Xiao-Geng
XG
Deng
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Yu
Y
Zhou
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Xiao
X
Ye
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Min
M
Yu
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Jing
J
Tang
Laboratory of Biomechanics and Physiology, Guangdong Provincial Institute of Sports Science, Guangzhou, Guangdong Province, China.
Xiao-Yu
XY
He
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Di
D
Cheng
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Bing
B
Zeng
Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Quan-bo
QB
Zhou
Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Zhi-hua
ZH
Li
D001483:Base Sequence; D063646:Carcinogenesis; D002453:Cell Cycle; D019938:Cyclin D1 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D016174:Hepacivirus; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D000071317:Nanog Homeobox Protein; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D014758:Viral Core Proteins / Q000378:metabolism*
D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050796:STAT3 Transcription Factor; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D019938:Cyclin D1
Hepatitis C virus core protein; Hepatocellular carcinoma; NANOG; Stat3 pathway