title: Original Research: Analysis of hepatic microRNA alterations in response to hepatitis B virus infection and pegylated interferon alpha-2a treatment.
abstract: Interferons play important roles in defense mechanisms against viral infection, and thus interferon therapy has been a standard treatment in chronic hepatitis B patients. Interferons signaling pathways promote interferon-inducible genes including microRNAs. In this research, we aimed to determine microRNAs expression profiles in vitro and in vivo For in vitro model, Huh7 cells were transfected with or without hepatitis B virus plasmid for 6 h, and then treated with 100 ng of pegylated-interferon alpha-2a for 24 h. In vivo, we defined microRNAs expression profiles in pair-liver tissues of chronic hepatitis B patients in comparison between before and after treatment of pegylated-interferon alpha-2a for 48 weeks. Cellular small RNAs were extracted followed by library preparation. To determine microRNAs expression profiles, the next-generation sequencing was carried out on MiSeq platform (Illumina®). In vitro analysis demonstrated that microRNAs can be classified into up-regulated and down-regulated microRNAs in response to hepatitis B virus, interferon, and combination of hepatitis B virus and interferon. Moreover, in vivo analysis revealed microRNAs profiles in non-responders, responders without hepatitis B surface antigen clearance, and responders with hepatitis B surface antigen clearance. The target genes of the candidate microRNAs were determined in terms of roles in cellular pathways and immune response, which might be related to treatment in chronic hepatitis B patients. Results revealed that two down-regulated microRNAs including miR-185-5p and miR-186-5p were correlated in both in vitro and in vivo studies. These two microRNAs might be represented as specific hepatic microRNAs responding to hepatitis B virus and pegylated-interferon alpha-2a treatment, which may remarkable and attractive for further study involving in the association of their target genes and prediction of pegylated-interferon alpha-2a response. Interestingly, microRNAs expression patterns might be useful for understanding the response mechanism and serve as biomarkers for prediction of pegylated-interferon alpha-2a treatment response in patients with chronic hepatitis B.
authors.affiliation: Systems Biology Center, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Thananya
authors.initials: T
authors.lastname: Jinato
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Natthaya
authors.initials: N
authors.lastname: Chuaypen
authors.affiliation: Systems Biology Center, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Witthaya
authors.initials: W
authors.lastname: Poomipak
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Kesmanee
authors.initials: K
authors.lastname: Praianantathavorn
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Jarika
authors.initials: J
authors.lastname: Makkoch
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Rattanaporn
authors.initials: R
authors.lastname: Kiatbumrung
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Kanisa
authors.initials: K
authors.lastname: Jampoka
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Pisit
authors.initials: P
authors.lastname: Tangkijvanich
authors.affiliation: Systems Biology Center, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand Research Unit of Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand sp.medbiochemcu@gmail.com.
authors.forename: Sunchai
authors.initials: S
authors.lastname: Payungporn
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D035683:MicroRNAs; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: hepatitis B virus; interferon; microRNA; next-generation sequencing