Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, PR China.
Hepatology. 2013 Feb;57(2):667-77. doi: 10.1002/hep.26071. Epub 2013 Jan 8.
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.
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.
据报道，微小 RNA（miRNAs）与癌症的发展有关。然而，miRNAs 在人肝细胞癌（HCC）中的功能在很大程度上尚未确定。在这里，我们发现 miR-10a 的过表达促进了 QGY-7703 和 HepG2 细胞在体外的迁移和侵袭，但抑制了体内的转移。细胞黏附实验表明，miR-10a 抑制了 HCC 细胞与基质的黏附，这可以解释体内动物实验的结果。Eph 酪氨酸激酶受体 EphA4 被鉴定为 miR-10a 的直接和功能靶基因。EphA4 的敲低模拟了 miR-10a 的作用，而 EphA4 的异位表达恢复了 miR-10a 对 HCC 细胞迁移、侵袭和黏附的作用。我们进一步证明，miR-10a 和 EphA4 通过调节上皮-间充质转化过程和β1-整合素途径来影响细胞侵袭和黏附。
我们的研究结果强调了 miR-10a 通过直接靶向 EphA4 调节 HCC 转移特性的重要性，并可能为 HCC 的发病机制提供新的见解。
