MicroRNA let-7g cooperates with interferon/ribavirin to repress hepatitis C virus replication.
MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
Wen-Wen
WW
Chou
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.|Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chung-Feng
CF
Huang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ming-Lun
ML
Yeh
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
Yi-Shan
YS
Tsai
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
Ming-Yen
MY
Hsieh
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
Ching-I
CI
Huang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.|Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jee-Fu
JF
Huang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
Pei-Chien
PC
Tsai
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Edward
E
Hsi
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Suh-Hang Hank
SH
Juo
Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|School of Medicine, National Yang Ming University, Taipei, Taiwan.
Wei-Lun
WL
Tsai
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.|Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wan-Long
WL
Chuang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.|Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ming-Lung
ML
Yu
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan. daichiayen@gmail.com.|Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. daichiayen@gmail.com.|Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. daichiayen@gmail.com.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. daichiayen@gmail.com.|Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. daichiayen@gmail.com.|Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. daichiayen@gmail.com.|Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. daichiayen@gmail.com.
Chia-Yen
CY
Dai
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D012254:Ribavirin
HCV; IFN; JFH; Let-7g; RBV