Mechanism of miR-424-5p promoter methylation in promoting epithelial-mesenchymal transition of hepatocellular carcinoma cells.
Kaohsiung J Med Sci
; 38(4): 336-346, 2022 Apr.
Article
en En
| MEDLINE
| ID: mdl-35049148
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Carcinoma Hepatocelular
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MicroARNs
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Neoplasias Hepáticas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Kaohsiung J Med Sci
Asunto de la revista:
MEDICINA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China