title: miR-218 modulate hepatocellular carcinoma cell proliferation through PTEN/AKT/PI3K pathway and HoxA10.
abstract: OBJECTIVE
  To investigate the regulatory mechanism of miR-218 in human hepatocellular carcinoma (HCC).
  
  
  METHODS
  qPCR was used to compare the expression levels miR-218 among six hepatocellular carcinoma cell lines and normal liver tissues. After transfecting MHCC97L cells with either miR-218 mimics or miR-218 inhibitor, western blotting was used to examine the expressing patterns of cyclinD1, p21, and PTEN/AKT/PI3K signaling pathway-related proteins. MTT and colony forming assay was used to assess the capability of cell proliferation. Bioinformatic method was applied to predict the binding of miR-218 on HoxA10, and western blotting was used to examine the modulatory effect of miR-218 AND HoxA10 on PTEN/AKT/PI3K pathway in HCC.
  
  
  RESULTS
  The expression levels of miR-218 were frequently lower in HCC cell lines than in normal liver tissues. Over-expression of miR-218 in HCC cells significantly decreased cell proliferation whereas inhibiting miR-218 promoted cancer cell proliferation. Western blotting analysis demonstrated that tumorigenesis related protein cyclin D1 and p21, as well as PTEN/AKT/PI3K signaling pathways were actively modulated by miR-218 in HCC cells. The expression of endogenous HoxA10 was also down-regulated by miR-218 over-expression, and silencing HoxA10 directly activated PTEN in HCC cells.
  
  
  CONCLUSIONS
  Modulation of miR-218 actively affected HCC cancer cell development. The regulatory mechanism of miR-218 in HCC cells was acting through PTEN/AKT/PI3K pathway and possibly associated with HoxA10.
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University Harbin 150001, China ; Department of General Surgery, Daqing Group Oilfield General Hospital Daqing 163001, China.
authors.forename: Zhong-Di
authors.initials: ZD
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, Daqing Group Oilfield General Hospital Daqing 163001, China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Jiao
authors.affiliation: Department of General Surgery, Daqing Group Oilfield General Hospital Daqing 163001, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Daqing Group Oilfield General Hospital Daqing 163001, China.
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: He
authors.affiliation: Department of General Surgery, Daqing Group Oilfield General Hospital Daqing 163001, China.
authors.forename: Jiu-Jun
authors.initials: JJ
authors.lastname: Zhao
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University Harbin 150001, China.
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Lu
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University Harbin 150001, China.
authors.forename: Lian-Xin
authors.initials: LX
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C547471:MIRN218 microRNA, human; C092119:Hoxa10 protein, mouse; C494929:PTEN protein, human
keywords: HoxA10; PTEN; hepatocellular carcinoma; miR-218