title: MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1α and PPARγ.
abstract: In hepatitis B virus (HBV)-replicating hepatocytes, miR-130a expression was significantly reduced. In a reciprocal manner, miR-130a reduced HBV replication by targeting at two major metabolic regulators PGC1α and PPARγ, both of which can potently stimulate HBV replication. We proposed a positive feed-forward loop between HBV, miR-130a, PPARγ, and PGC1α. Accordingly, HBV can significantly enhance viral replication by reducing miR-130a and increasing PGC1α and PPARγ. NF-κB/p65 can strongly stimulate miR-130a promoter, while miR-130a can promote NF-κB/p65 protein level by reducing PPARγ and thus NF-κB/p65 protein degradation. We postulated another positive feed-forward loop between miR-130a and NF-κB/p65 via PPARγ. During liver inflammation, NF-κB signaling could contribute to viral clearance via its positive effect on miR-130a transcription. Conversely, in asymptomatic HBV carriers, persistent viral infection could reduce miR-130a and NF-κB expression, leading to dampened inflammation and immune tolerance. Finally, miR-130a could contribute to metabolic homeostasis by dual targeting PGC1α and PPARγ simultaneously.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 114 Taiwan Institute of Biomedical Sciences, Academia Sinica, Taipei, 115 Taiwan.
authors.forename: Jyun-Yuan
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 115 Taiwan Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, 110 Taiwan.
authors.forename: Shu-Fan
authors.initials: SF
authors.lastname: Chou
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 115 Taiwan.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 115 Taiwan.
authors.forename: Hung-Lin
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 115 Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 115 Taiwan.
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Tao
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 114 Taiwan Institute of Biomedical Sciences, Academia Sinica, Taipei, 115 Taiwan cshih@ibms.sinica.edu.tw.
authors.forename: Chiaho
authors.initials: C
authors.lastname: Shih
mesh_terms: D004261:DNA Replication / Q000235:genetics; D005786:Gene Expression Regulation; D006509:Hepatitis B / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors
keywords: PGC1α; PPARγ; hepatitis B virus; inflammation; microRNA