title: MicroRNA-125b-5p mediates post-transcriptional regulation of hepatitis B virus replication via the LIN28B/let-7 axis.
abstract: MicroRNAs (miRNAs) are able to modulate hepatitis B virus (HBV) replication and play an important role in the pathogenesis of HBV infection. Recently, we have identified that serum miR-125b-5p levels correlated with HBV DNA levels and liver necroinflammation. In the present study, we addressed how miR-125b-5p regulated HBV replication at the different steps, inclduing viral transcription, assembly, and virion production and investigated the underlying mechanisms. We found that miR-125b-5p overexpression increased HBV replication without altering HBV transcription. This is the first demonstration of post-transcriptional miRNA regulation of HBV replication. In contrast, transfection of miR-125b-5p inhibitor resulted in downregulation of HBV replication in hepatoma cells. Further, miR-125b-5p inhibited the phosphorylation of retinoblastoma protein and blocked cell cycle progression at the G1/S phase in hepatoma cell lines. Our results indicate that certain miRNAs are able to arrest the cell cycle at G1 phase and may increase HBV replication. RNA sequencing revealed several liver-specific metabolic pathways regulated by miR-125b-5p, which was also found to suppress LIN28B and induce let-7 family members. Additional data demonstrated that miR-125b-5p targeted the LIN28B/let-7 axis to stimulate HBV replication at a post-transcriptional step.
authors.affiliation: a Institute of Virology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany.|b College of Life Science, Shangrao Normal University , Shangrao , China.
authors.forename: Wanyu
authors.identifier: 0000-0001-7789-3861
authors.initials: W
authors.lastname: Deng
authors.affiliation: a Institute of Virology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Institute of Virology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: a Institute of Virology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany.
authors.forename: Yong
authors.identifier: 0000-0001-9171-0195
authors.initials: Y
authors.lastname: Lin
authors.affiliation: a Institute of Virology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
mesh_terms: D002453:Cell Cycle; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000821:virology; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000235:genetics*; D009928:Organ Specificity; D010766:Phosphorylation; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics*; D056286:Retinoblastoma Binding Proteins / Q000378:metabolism; D017423:Sequence Analysis, RNA; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014779:Virus Replication
chemical_list: C516326:LIN28B protein, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C000606393:RB1 protein, human; D016601:RNA-Binding Proteins; D056286:Retinoblastoma Binding Proteins; C487931:mirnlet7 microRNA, human; D044767:Ubiquitin-Protein Ligases
keywords: Hepatitis B virus; LIN28B; hepatoma cell; metabolism; microRNA