title: Derepression of c-Fos caused by microRNA-139 down-regulation contributes to the metastasis of human hepatocellular carcinoma.
abstract: This study investigates whether the anti-metastasis effect of microRNA-139 (miR-139) on hepatocellular carcinoma (HCC) is mediated through regulating c-fos expression. The expression levels of miR-139 and c-fos in human HCC cell sublines with high (MHCC97H) and low (MHCC97L) spontaneous metastatic potentials were quantified using QPCR or Western blot. miR-139 mimics was transfected into MHCC97H cells to overexpress miR-139, and miR-139 inhibitor was transfected into MHCC97L cells to down-express miR-139. The effect of overexpression or down-expression of miR-139 on c-fos expression of MHCC97H and MHCC97L cells was evaluated using QPCR and Western blot. The 3' untranslated region segments of FOS containing the miR-139 binding sites were amplified by PCR, and the luciferase activity in the transfected cells was assayed. In comparison with the expression level of miR-139 in MHCC97L cells, the expression level in MHCC97H cells was significantly decreased, whereas c-Fos was significantly up-regulated in MHCC97H. The overexpression of miR-139 significantly inhibited the expression of c-fos in MHCC97H cells, and the down-expression of miR-139 significantly promoted the expression of c-fos in MHCC97L cells. miR-139 suppressed the luciferase activity of the pGL-FOS by approximately 40% compared with the negative control. In vitro cell migration analysis demonstrated that depletion of c-fos or overexpression of miR-139 in MHCC97H cells reduced cell migration, whereas overexpression of c-fos or depletion of miR-139 in MHCC97L cells increased cell migration. Thus, we got the conclusion that miR-139 expression is down-regulated in human HCC cell sublines with high spontaneous metastatic potentials (MHCC97H). Derepression of c-Fos caused by miR-139 down-regulation contributes to the metastasis of HCC.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fan
authors.forename: Minyi
authors.initials: M
authors.lastname: He
authors.forename: Xinjun
authors.initials: X
authors.lastname: Deng
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.forename: Ge
authors.initials: G
authors.lastname: Wen
authors.forename: Xuegang
authors.initials: X
authors.lastname: Sun
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism
chemical_list: C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D016760:Proto-Oncogene Proteins c-fos