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 b1-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. (HEPATOLOGY 2013;57:667-677)
Background: Recent research has uncovered tumor suppressive and oncogenic potential of miRNAs. Results: miR-941 expression is regulated by DNA methylation, and is an important regulator of cell proliferation, migration, and invasion by directly targeting KDM6B in hepatocellular carcinoma (HCC). Conclusion: miR-941 may play an important role in suppressing tumor growth and metastasis in HCC. Significance: miR-941 may provide a potential biomarker for the diagnosis and treatment of HCC.
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