title: MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma.
abstract: MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. Recently, microRNA-373 (miR-373) has been found to function as an oncogene in testicular germ cell tumors. In our study, we found that miR-373 is upregulated in human hepatocellular carcinoma (HCC) tissues as compared with adjacent normal tissues, and promotes the proliferation of the HCC cell lines HepG2 and QGY-7703 by regulating the transition between G(1)-phase and S-phase. The gene encoding the protein phosphatase 6 catalytic subunit (PPP6C ), a negative cell cycle regulator, was identified as a direct target gene of miR-373 by use of a fluorescent reporter assay. The mRNA and protein levels of PPP6C were both inversely correlated with the miR-373 expression level. Overexpression of PPP6C abolished the regulation of cell cycle and cell growth exercised by miR-373 in HepG2 cells. These results indicate that miR-373 plays an important role in the pathogenesis of HCC, and may be a new biomarker in HCC. Our results demonstrate that miR-373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of HCC cells in vitro. The downregulation of PPP6C by miR-373 may explain why the expression of miR-373 can promote HCC cell proliferation.
authors.affiliation: Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Wu
authors.forename: Xuyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Xu
authors.forename: Xingxing
authors.initials: X
authors.lastname: Fan
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zhong
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D009857:Oncogenes; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C527114:MIRN373 microRNA, human; D035683:MicroRNAs; D020319:Oligodeoxyribonucleotides, Antisense; D010749:Phosphoprotein Phosphatases; C106079:protein phosphatase 6