title: miR-122 inhibits viral replication and cell proliferation in hepatitis B virus-related hepatocellular carcinoma and targets NDRG3.
abstract: microRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory functions that participate in diverse biological pathways. miR-122, a liver-specific miRNA, has been found to be down-regulated in hepatocellular carcinoma (HCC) and HCC-derived cell lines. In this study, miR-122 was down-regulated in the hepatitis B virus (HBV)-related HCC cell line HepG2.2.15 compared to HepG2. NDRG3, a member of the N-myc downstream-regulated gene (NDRG) family, was up-regulated in HepG2.2.15 and was identified as a target gene of miR-122. An inverse correlation between the expression of miR-122 and the NDRG3 protein was noted in HBV-related HCC specimens. The transfection of the miR-122 expression vector into the HepG2.2.15 cell line repressed the transcription and expression of NDRG3, which subsequently reversed the malignant phenotype of the cells. The replication of HBV, expression of viral antigens and proliferation of cells were significantly inhibited by restoration of miR-122. The data demonstrate that miR-122 plays an important role in HBV-related hepatocarcinogenesis by targeting NDRG3. Thus, miR-122 and NDRG3 represent key diagnostic markers and potential therapeutic targets for HBV-related HCC.
authors: Department of Pathophysiology, Shandong University School of Medicine, Jinan, PR China.
authors: Chun-Guang
authors: CG
authors: Fan
authors: Chun-Mei
authors: CM
authors: Wang
authors: Chuan
authors: C
authors: Tian
authors: Yan
authors: Y
authors: Wang
authors: Li
authors: L
authors: Li
authors: Wen-Sheng
authors: WS
authors: Sun
authors: Rui-Feng
authors: RF
authors: Li
authors: Yu-Gang
authors: YG
authors: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014779:Virus Replication / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C431706:NDRG3 protein, human; D009419:Nerve Tissue Proteins