Regulation of the oncogenic function of distal-less 4 by microRNA-122 in hepatocellular carcinoma

Distal-less 4 (DLX4) is a member of the DLX family of homeobox genes. Recent reports have suggested that abnormal expression of DLX4 is present in several types of human tumors, including breast cancer, leukemia and colon cancer. However, the function and the mechanistic regulation of DLX4 in hepatocellular carcinoma (HCC) are elusive. In the present study, a proportion of hepatocellular carcinomas were identified to exhibit upregulated DLX4 expression. This study proposed that the overexpression of DLX4 is associated with the downregulation of miR-122, an underexpressed miRNA in human HCC. Functional studies have demonstrated that the downregulation of DLX4 in hepatocellular carcinoma cell lines is regulated by miR-122 through binding to its 3'UTR. Furthermore, a DLX4 overexpression vector lacking the 3'UTR was shown to abolish miR-122-induced inhibition of proliferation in the HCC cell line Hep3B. These results gave new insight into the mechanism of the miR-122/DLX4 axis in HCC.