title: Regulation of the microRNA processor DGCR8 by hepatitis B virus proteins via the transcription factor YY1.
abstract: MicroRNAs (miRNAs) are a new class of well-conserved small noncoding RNAs that mediate posttranscriptional gene regulation. Hepatitis B virus (HBV) causes various liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular cancer. Recent data have indicated HBV alters miRNAs expression patterns, but the underlying mechanisms have not been fully established so far. Here, we provide a hypothesis that HBV alters the expressions of miRNAs by playing a role in the microRNA production process. In this study, we demonstrate that HBV downregulates miRNAs processor DGCR8 mRNA and protein expression in stable and transient HBV-expressing cells. HBV downregulates DGCR8 expression by inhibiting its promoter activity, and HBs and HBx may be involved in this process. Ectopic expression and knockdown of YY1 revealed that YY1 suppresses the activity of the DGCR8 promoter, while YY1 expression is significantly upregulated by HBV. In conclusion, our data show that HBV proteins repress DGCR8 promoter activity by upregulating the expression of transcription factor YY1. This provides a new insight into the mechanism of HBV-induced miRNA dysregulation.
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Shan
authors.forename: Min
authors.initials: M
authors.lastname: Ren
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Ailong
authors.initials: A
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: C474043:DGCR8 protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human