miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma.

Background and Aim Micro RNAs (mi RNAs) are small noncoding RNA molecules that control target gene expression and are implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated that mi R-224 was overexpressed in liver cancer cells and tissues, which was an important factor in the regulation of cell migration and invasion. This study aimed to further explore the regulatory mechanism of mi R-224 in the migration and invasion in liver cancer cells. Methods A luciferase reporter assay was used to confirm that the HOXD10 gene was a direct target of mi R-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of mi R-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma ( HCC). Results (i) The expression of mi R-224 was strongly upregulated in MHHC97 H and MHCC97 L cells, and its expression level was significantly associated with cell invasive potential. (ii) The HOXD10 gene was confirmed to be a direct target of mi R-224. Compared with normal liver tissues and cells, HOXD10 had lower expression in HCC tissues and cells and inversely regulated HCC cell invasion. (iii) mi R-224 promoted expression of the tumor invasion-associated proteins p- PAK4 and MMP-9 by directly targeting HOXD10. Conclusion Our findings suggest a previously undescribed regulatory pathway in which the mi R-224/ HOXD10/p- PAK4/ MMP-9 signaling pathway contributes to the regulation of cell migration and invasion and provides a new biotarget for HCC treatment. [ABSTRACT FROM AUTHOR]