*These authors contributed equally to this work
Article first published online: 8 JAN 2013
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 57, Issue 2, pages 667–677, February 2013
How to Cite
Yan, Y., Luo, Y.-C., Wan, H.-Y., Wang, J., Zhang, P.-P., Liu, M., Li, X., Li, S. and Tang, H. (2013), MicroRNA-10a is involved in the metastatic process by regulating Eph tyrosine kinase receptor A4-Mediated epithelial-mesenchymal transition and adhesion in hepatoma cells. Hepatology, 57: 667–677. doi: 10.1002/hep.26071
Potential conflict of interest: Nothing to report.
Supported by the National Natural Science Foundation of China (numbers 30873017; 91029714; 31071191; 31101000) and the Natural Science Foundation of Tianjin (09JCZDJC17500; 12JCZDJC25100).
- Issue published online: 5 FEB 2013
- Article first published online: 8 JAN 2013
- Accepted manuscript online: 19 SEP 2012 11:32AM EST
- Manuscript Accepted: 5 SEP 2012
- Manuscript Received: 17 MAR 2012
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. (HEPATOLOGY 2013)