1, 2 miRNAs can function as tumor suppressors or oncogenes, depending on whether they specifically target oncogenes or tumor suppressor genes.3-5 Recently, studies on tumor invasion, metastasis, and adhesion have revealed a critical role of miRNAs in these processes.6-9 Some studies have also focused on the effect of miRNAs on the migration and invasion of hepatocellular carcinoma (HCC) cells. miR-34a and Let-7g inhibit, whereas miR-30d, miR-17-5p, and miR-151 promote cell migration and invasion in HCC cells.10-14 miR-10b, a member of the miRNA family that contains miR-10, miR-51, miR-57, miR-99, and miR-100

(miBase website) can regulate metastasis of breast cancer.15 selleck inhibitor We asked whether miR-10a is involved in the process of cancer metastasis. In this study we investigated whether miR-10a also contributed to the metastasis of HCC cells. HCC is a highly malignant tumor with very poor prognosis, and invasion and migration to other tissue sites are the primary causes of mortality in patients with solid tumors.16, 17 Recent studies have suggested that CX-4945 chemical structure the specific site of cancer cell metastasis does not depend on the anatomic location of the primary tumor or its proximity to secondary sites, but rather, it involves interactions between tumor cells and the local microenvironment at the secondary site, such as cell-matrix adhesion.18 Epithelial-mesenchymal

transition (EMT) is the key process that drives cancer metastasis and it is characterized by loss of the epithelial marker E-cadherin, increased expression of the mesenchymal marker vimentin, and enhanced migratory and invasive behaviors.19 Barrios et al.20 indicated that Eph tyrosine kinase receptor A4 (EphA4) regulates the mesenchymal-to-epithelial transition (MET) of the paraxial mesoderm during somite morphogenesis. The Eph receptors represent the largest family of receptor protein tyrosine kinases and they interact with their ligands, ephrins. Most recently, the genes for Eph receptors and ephrins have been demonstrated to be differentially expressed in various

human tumors.21-27 EphA4 is a member of the Eph receptor tyrosine kinase family and has been reported to play roles in different types of human cancers. EphA4 promotes cell proliferation MCE公司 and migration through an EphA4-FGFR1 signaling pathway in the human glioma U251 cell line.28 Overexpression of the EphA4 gene and reduced expression of the EphB2 gene correlate with liver metastasis in colorectal cancer.29 However, EphA4 has never been described in association with HCC. In this study we found that miR-10a promoted the migration and invasion of the human HCC cell lines QGY-7703 and HepG2 but suppressed the metastasis of HCC cells in in vivo metastasis assays. We identified EphA4 as a direct target of miR-10a.