title: MicroRNA-141 represses HBV replication by targeting PPARA.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression primarily at the post-transcriptional level and play critical roles in a variety of physiological and pathological processes. In this report, miR-141 was identified to repress HBV expression by screening a small miRNA expressing library and synthetic miR-141 mimics could also significantly suppress HBV expression and replication in HepG2 cells. Bioinformatic analysis and experiment assays indicate that peroxisome proliferator-activated receptor alpha (PPARA) was the target of hsa-miR-141 during this process. Furthermore, knockdown of PPARA by small interfering RNA (siRNA) inhibited HBV replication similar to levels observed for miR-141. Promoter functional analysis indicated that repression of HBV replication by miR-141 mimics or siRNA was mediated by interfering with the HBV promoter functions, consistent with previous studies demonstrating that PPARA regulated HBV gene expression through interactions with HBV promoter regulatory elements. Our results suggest that miR-141 suppressed HBV replication by reducing HBV promoter activities by down-regulating PPARA. This study provides new insights into the molecular mechanisms associated with HBV-host interactions. Furthermore, this information may facilitate the development of novel anti-HBV therapeutic strategies.
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Ding
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Peiwen
authors.initials: P
authors.lastname: Xie
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Shengqi
authors.initials: S
authors.lastname: Wang
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014779:Virus Replication
chemical_list: C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D047493:PPAR alpha