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MicroRNA‐10a is involved in the metastatic process by regulating Eph tyrosine kinase receptor A4‐Mediated epithelial‐mesenchymal transition and adhesion in hepatoma cells *
Author(s) -
Yan Yan,
Luo YueChen,
Wan HaiYing,
Wang Jun,
Zhang PeiPei,
Liu Min,
Li Xin,
Li Shengping,
Tang Hua
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26071
Subject(s) - erythropoietin producing hepatocellular (eph) receptor , epithelial–mesenchymal transition , cancer research , focal adhesion , gene knockdown , microrna , cell adhesion , cell migration , receptor tyrosine kinase , metastasis , microbiology and biotechnology , tyrosine kinase , biology , integrin , invadopodia , signal transduction , cell , cell culture , cancer , gene , biochemistry , genetics
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. Conclusion: 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. (H EPATOLOGY 2013)