miR-22 Suppresses Epithelial-Mesenchymal Transition by Modulating Snail and MAPK1 in Hepatocellular Carcinoma

Abstract Background: Recently studies have reported that miR-22 plays an important role in epithelial-mesenchymal transition (EMT) of many human cancers. However, the involvement of miR-22 in hepatocellular carcinomas (HCC) EMT progression has not been investigated. Methods: We measured miR-22 expression level in 38 paired of HCC and matched normal tissues by real-time quantitative RT-PCR. Then, we performed morphological analysis and immunofluorescence to observe the role of miR-22 in HCC EMT progression. The expression of EMT markers were detected by real-time RT-PCR and western blot. The regulation role of miR-22 on Snail, mitogen-activated protein kinase 1(MAPK1) and slug were determined by luciferase reporter assay. The expression of Snail and MAPK1 were also detected by real-time quantitative RT-PCR in HCC and normal tissues. Results: We found that the expression of miR-22 in HCC tissues were much lower than that in normal control. The expression of miR-22 was inversely correlated with HCC metastatic ability. Then, we found that overexpression of miR-22 could inhibit HCC EMT. Importantly, miR-22 is found to inhibit cell motility by directly targeting both Snail and MAPK1. Furthermore, the suppression role of miR-22 in HCC EMT could be blocked by Snail and MAPK1 overexpression. Additionally, the expression of Snail and MAPK1 were inversely correlated with miR-22 expression in HCC tissues. Conclusion: Our results suggested that miR-22 was downexpressed in HCC tissues and inhibited HCC EMT through downregulating Snail and MAPK1 which may provide a new bio-target for HCC therapy.