title: MicroRNA miR-204 and miR-1236 inhibit hepatitis B virus replication via two different mechanisms.
abstract: Hepatitis B virus (HBV) is a major human pathogen. In this study, we found that miR-204 and miR-1236 were down-regulated in HBV-producing cells, and each could suppress HBV replication. Using a bioinformatic approach and a reporter assay, we identified miR-1236, which can reduce HBV replication and protein production by directly targeting at HBV specific mRNA. In contrast, miR-204 was identified by a microarray approach, and had no effect on HBV RNA and protein production. Surprisingly, miR-204 could inhibit HBV pregenomic RNA encapsidation and capsid assembly. We further demonstrated that HBV suppressed miR-204 expression via activating a host transcription factor STAT3. We established a positive feed-forward loop between HBV, miR-204 and STAT3. Interestingly, miR-204 has been considered as a tumor suppressor in some literature. Since the risk for hepatocellular carcinoma (HCC) is significantly increased in chronic HBV patients, it is possible that chronic suppression of miR-204 by HBV contributes to HCC incidence. Both miR-204 and miR-1236 might be useful for developing new therapeutics against HBV.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Jyun-Yuan
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hung-Lin
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chiaho
authors.initials: C
authors.lastname: Shih
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D019295:Computational Biology; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: C571208:MIRN1236 microRNA, human; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human