E2F1-induced microRNA-224-5p expression is associated with hepatocellular carcinoma cell migration, invasion and epithelial-mesenchymal transition via MREG.

Abstract

MicroRNA (miR)-224-5p has been reported to be associated with multiple types of cancer. However, its biological role and underlying mechanism in hepatocellular carcinoma (HCC) has yet to be fully elucidated. The aim of the present study was to investigate whether miR-224-5p mRNA expression level was increased in hepatocellular carcinoma and whether it was associated with poor prognosis. Decreased mRNA expression level of miR-224-5p was shown to suppress liver cancer cell migration, invasion and epithelial-mesenchymal transition (EMT). Mechanistically, E2F1 was found to regulate miR-224-5p expression by binding to its promoter region. Melanoregulin (MREG) was identified as the direct target of miR-224-5p by searching the TargetScan, miRDB and StarBase databases. Overexpression of MREG could attenuate liver cancer cell migration, invasion and EMT. Rescue experiments further confirmed that MREG was associated with the regulation of miR-224-5p in liver cancer. In addition, the E2F1/miR-224-5p axis was shown to promote liver cancer cell migration, invasion and EMT by regulating MREG expression. These results suggested that E2F1-induced upregulation of miR-224-5p may serve an important role in MREG-induced liver cancer cell migration, invasion and EMT, and highlights the regulatory function of miR-224-5p in liver cancer. Therefore, the E2F1/miR-224-5p/MREG axis may provide a theoretical basis for the clinical treatment of hepatocellular carcinoma.