3,4 Dihydroxyphenylethanol May Inhibit Metastasis in HepG2 Cells by Influencing the Expression of miR-21 and Genes Associated with Metastasis

Background: Hepatocellular carcinoma (HCC) is one of the lethal malignancies with a poor prognosis due to metastatic complications. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have an important role in metastasis. MicroRNA-21 (miR-21) is significantly overexpressed in nearly all types of human cancers, including HCC. Targeting miR-21 pharmacologically could be a promising therapeutic approach for HCC. 3,4-dihydroxyphenylethanol (DHPE), a phenolic phytochemical compound found in olive, has potent antioxidant and anticancer properties. This study aimed to investigate the effect of DHPE on the expression of miR-21 with genes associated with metastasis (MMP-2, MMP-9, TIMP-1, and TIMP-2) and their correlation with miR-21 in HepG2 cells. Methods: This experimental study had four groups, including a control, and three groups of treatment with different concentrations of DHPE (50, 100, and 150 µM) for 24 hours. The expression levels of genes were determined by RT-qPCR. Results: The results showed that the treatment of cells with DHPE significantly reduced the expression of miR-21, MMP-2, MMP-9, and TIMP-1 but increased TIMP-2 compared to the control group; additionally, there was a negative correlation between miR-21 and TIMP-2 but a positive correlation between miR-21 with MMP-2, MMP-9, and TIMP-1. Conclusions: The results showed that DHPE, likely by reducing the expression of miR-21, can increase TIMP-2 and reduce MMP-2, MMP-9, and TIMP-1 gene expression and may play a role in inhibiting cell migration in HepG2 cells.