title: HBx down-regulated Gld2 plays a critical role in HBV-related dysregulation of miR-122.
abstract: miR-122 is a liver-rich-specific microRNA that plays an important role in hepatic gene expression via post-transcription regulation, and it is potentially associated with the development of hepatocellular carcinoma. It has been confirmed that miR-122 is down-regulated during HBV infection; however, how HBV affects miR-122 is still debated. One research provided evidence that HBx could reduce the miR-122 transcription level, but the other insisted that HBV had no significant effect on miR-122 transcription level but reduce miR-122 level via binding and sequestering endogenous miR-122. It is determinate that Gld2 could increase the specific miRNA stabilization by monoadenylation which was a post-transcription regulation. In this study, we aimed to investigate the mechanism of HBV-induced reduction of miR-122 and examine whether Gld2 is involved in it. According to the results of a microRNA microarray, we found miR-122 was the most down-regulated microRNA in HepG2.2.15 compared to HepG2. As revealed by qRT-PCR and western blotting analyses, both miR-122 and Gld2 levels were reduced in hepatic cell lines with expression of HBV or HBx but not other proteins of HBV, and over-expression of Gld2 could abolish the effect of HBV and HBx on the miR-122 level. What's more, both HBV and HBx have no significant effect on pre-miR-122 levels. And the dual-luciferase assay implicated that HBx could reduce the Gld2 promoter activity but had no significant effect on miR-122 promoter activity. In conclusion, HBx is a critical protein derived from HBV, which regulates miR-122 via down-regulating Gld2.
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Kaizhong
authors.initials: K
authors.lastname: Luo
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Milin
authors.initials: M
authors.lastname: Peng
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Gong
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D006515:Hepatitis B virus / Q000378:metabolism / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011062:Polynucleotide Adenylyltransferase; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D039221:mRNA Cleavage and Polyadenylation Factors; D011062:Polynucleotide Adenylyltransferase; C550174:TENT2 protein, human