title: Prognostic significance of miR-218 in human hepatocellular carcinoma and its role in cell growth.
abstract: MicroRNA-218 (miR-218) is considered a tumor suppressor in human cancer. In the present study, miR-218 expression was found to be significantly lower in human hepatocellular carcinoma (HCC) than in normal tumor-adjacent tissues. miR-218 was clearly silenced or downregulated in five HCC cells (HepG2, Hep3B, SMMC-7721, Huh7 and Bel-7402) compared with normal hepatocytes (LO2). The low expression of miR-218 conferred a poor 5-year survival in HCC patients. Multivariate Cox regression analysis indicated that miR-218 was an independent prognostic factor in HCC. Ectopic expression of miR-218 inhibited proliferation and promoted apoptosis in HepG2 and SMMC-7721 cells. In tumor bearing mice, miR-218 slowed down tumor growth by inducing apoptosis and growth arrest. Restoring miR-218 expression resulted in downregulation of B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) mRNA and protein level in HepG2 and SMMC-7721 cells. In addition, BMI-1 mRNA expression in HCC was significantly higher than that in non-cancerous tissues. BMI-1 mRNA was inversely correlated with miR-218 expression in HCC tissues. In conclusion, miR-218 may serve as a prognostic biomarker and induce apoptosis and growth arrest by downregulating BMI-1 in HCC.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Tu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qingguang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C069077:BMI1 protein, human; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D063150:Polycomb Repressive Complex 1