۳,۴ Dihydroxyphenylethanol May Inhibit Metastasis in HepG۲ Cells by Influencing the Expression of miR-۲۱ 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-۲۱ (miR-۲۱) is significantly overexpressed in nearly all types of human cancers, including HCC. Targeting miR-۲۱ pharmacologically could be a promising therapeutic approach for HCC. ۳,۴-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-۲۱ with genes associated with metastasis (MMP-۲, MMP-۹, TIMP-۱, and TIMP-۲) and their correlation with miR-۲۱ in HepG۲ cells. Methods: This experimental study had four groups, including a control, and three groups of treatment with different concentrations of DHPE (۵۰, ۱۰۰, and ۱۵۰ µM) for ۲۴ 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-۲۱, MMP-۲, MMP-۹, and TIMP-۱ but increased TIMP-۲ compared to the control group; additionally, there was a negative correlation between miR-۲۱ and TIMP-۲ but a positive correlation between miR-۲۱ with MMP-۲, MMP-۹, and TIMP-۱. Conclusion: The results showed that DHPE, likely by reducing the expression of miR-۲۱, can increase TIMP-۲ and reduce MMP-۲, MMP-۹, and TIMP-۱ gene expression and may play a role in inhibiting cell migration in HepG۲ cells.

کلیدواژه ها:

HepG۲ cells ، miR-۲۱ ، Matrix Metalloproteinases ، Tissue Inhibitor of Metalloproteinases ، ۳ ، ۴-Dihydroxyphenylethanol.