miR-301a Is a Candidate Oncogene that Targets the Homeobox Gene Gax in Human Hepatocellular Carcinoma

MicroRNAs (miRNA) are a group of noncoding small RNAs that repress mRNA expression or induce mRNA degradation by binding to the 3'-untranslated regions of mRNAs. MiRNAs have been connected closely with the development of cancers such as hepatocellular carcinoma (HCC). However, the overexpression of microRNA-301a (miR-301a) has seldom been connected with tumorigenesis in HCC. This study aims to characterize the function of upregulated miR-301a in HCC and show how the downstream growth arrest-specific homeobox (Gax) is negatively regulated by miR-301a. The expression of miR-301a and Gax was detected using real-time PCR on HCC tissues and adjacent non-tumorous tissues. The luciferase reporter assay was used to assess Gax as a target of miR-301a. The nuclear factor kappa B (NF-kappa B) was measured by western blot after inhibiting miR-301a and enhancing Gax. The functions of miR-301a in vivo in HCC cells were measured by migration and invasion assays and flow cytometry. MiR-301a was significantly upregulated and Gax was downregulated in HCC samples compared with in the matching nontumoral tissues. Inhibiting miR-301a expression caused the upregulation of Gax and repressed NF-kappa B expression. We have shown that miR-301a plays an important role in increasing proliferation, migration and invasion and in inhibiting apoptosis of HCC cells. miR-301a is frequently upregulated in HCC and modulates NF-kappa B expression by negatively regulating Gax.