Mechanism of miR-424-5p promoter methylation in promoting epithelial-mesenchymal transition of hepatocellular carcinoma cells

The current study set out to clarify the role of miR-424-5p promoter methylation in epithelial mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. The findings of quantitative real-time-polymerase chain reaction and methylation-sensitive high-resolution melting assays elicited that miR-424-5p was poorly expressed in HCC tissues and cells while highly methylated. Meanwhile, upon demethylation, miR-424-5p expression levels were partly recovered in HCC cells. In addition, miR-424-5p upregulation reduced cell viability and elevated apoptosis of HCC cells, in parallel with increased N-cadherin and decreased E-cadherin levels. Dual-luciferase reporter assay further validated that miR-424-5p bound to the kinesin family member 2A (KIF2A), and miR-424-5p overexpression downregulated KIF2A. In addition, KIF2A overexpression reversed the miR-424-5p-driven changes in terms of cell viability, apoptosis and EMT-related protein levels. Furthermore, xenograft tumors were established via injection of Huh7 cells, followed by miR-424-5p overexpression in vivo, which inhabited KIF2A downregulation and attenuated tumor growth along with decreased Ki67 positive expression, diminished N-cadherin and elevated E-cadherin levels. Overall, our findings supported the conclusion that miR-424-5p promoter methylation reduced miR-424-5p expression and upregulated KIF2A, thereby promoting HCC EMT.

Automated summary

The current study aimed to investigate the role of miR-424-5p promoter methylation in epithelial mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. The results showed that miR-424-5p was poorly expressed and highly methylated in HCC tissues and cells. Upregulation of miR-424-5p reduced cell viability and increased apoptosis, accompanied by changes in N-cadherin and E-cadherin levels. Further experiments revealed that miR-424-5p interacted with KIF2A and downregulated its expression. In vivo studies showed that miR-424-5p overexpression inhibited KIF2A downregulation and attenuated tumor growth.