HBx elevates oncoprotein AEG-1 expression to promote cell migration by downregulating miR-375 and miR-136 in malignant hepatocytes

The hepatitis B viral X protein (HBx) has been established to implicate in the development of HBV-related hepatocellular carcinoma (HCC) via multiple pathways. The oncoprotein astrocyte elevated gene-1 (AEG-1) is overexpressed in various tumors, including HCC, and plays critical roles in promoting cell migration and invasion. However, the mechanisms for AEG-1 upregulation in tumors are largely unknown. In this study, we found that HBx could elevate AEG-1 protein level without altering its mRNA level. When blocking AEG-1 expression with siRNA in HBx-transfected cells, the HBx-induced cell migration was significantly suppressed. Further study indicated that miR-375 and miR-136 that targeted AEG-1 were downregulated with HBx expression. Overexpressing miR-375 and miR-136 could effectively attenuate HBx-mediated AEG-1 elevation and cell migration. These results demonstrated that HBx enabled to increase oncoprotein AEG-1 expression to promote cell migration via downregulating miR-375 and miR-136. Our findings provide a novel insight into AEG-1 upregulation in HCC and shed new light on HBx promoting HCC progression. Meanwhile, our results also suggest that miR-375 and miR-136 may have the miRNA-based therapeutic potential in HBV-associated HCC.