title: MicroRNA-10a is involved in the metastatic process by regulating Eph tyrosine kinase receptor A4-mediated epithelial-mesenchymal transition and adhesion in hepatoma cells.
abstract: MicroRNAs (miRNAs) have been reported to be associated with the development of cancers. However, the function of miRNAs in human hepatocellular carcinoma (HCC) remains largely undefined. Here we found that overexpression of miR-10a promoted the migration and invasion of QGY-7703 and HepG2 cells in vitro but suppressed metastasis in vivo. Cell adhesion assays showed that miR-10a suppressed HCC cell-matrix adhesion, which could explain the results of the in vivo animal experiments. The Eph tyrosine kinase receptor, EphA4, was identified as the direct and functional target gene of miR-10a. Knockdown of EphA4 phenocopied the effect of miR-10a and ectopic expression of EphA4 restored the effect of miR-10a on migration, invasion, and adhesion in HCC cells. We further demonstrated that miR-10a and EphA4 regulated the epithelial-mesenchymal transition process and the β1-integrin pathway to affect cell invasion and adhesion.
  
  
  CONCLUSIONS
  Our findings highlight the importance of miR-10a in regulating the metastatic properties of HCC by directly targeting EphA4 and may provide new insights into the pathogenesis of HCC.
authors.affiliation: Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Yue-Chen
authors.initials: YC
authors.lastname: Luo
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Wan
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Shengping
authors.initials: S
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000556:secondary*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D021982:Cell-Matrix Junctions / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D036122:Receptor, EphA4 / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D036122:Receptor, EphA4