Open AccessMechanism of miR ‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells
Author(s) -
Lv HongCheng,
Lv YanYan,
Wang Gang,
Zhang XieHua,
Li ShengNan,
Yue XiaoFen,
Lu Wei
Publication year - 2022
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12499
Subject(s) - downregulation and upregulation , methylation , epithelial–mesenchymal transition , hepatocellular carcinoma , apoptosis , cancer research , viability assay , dna methylation , medicine , microbiology and biotechnology , biology , gene expression , gene , biochemistry
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.