Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells
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 elic...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12499 |
| _version_ | 1811272632388026368 |
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| author | Hong‐Cheng Lv Yan‐Yan Lv Gang Wang Xie‐Hua Zhang Sheng‐Nan Li Xiao‐Fen Yue Wei Lu |
| author_facet | Hong‐Cheng Lv Yan‐Yan Lv Gang Wang Xie‐Hua Zhang Sheng‐Nan Li Xiao‐Fen Yue Wei Lu |
| author_sort | Hong‐Cheng Lv |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T22:43:51Z |
| format | Article |
| id | doaj.art-7bd874837e0e494b9c6d0a12a25ac2b9 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-04-12T22:43:51Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-7bd874837e0e494b9c6d0a12a25ac2b92022-12-22T03:13:38ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502022-04-0138433634610.1002/kjm2.12499Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cellsHong‐Cheng Lv0Yan‐Yan Lv1Gang Wang2Xie‐Hua Zhang3Sheng‐Nan Li4Xiao‐Fen Yue5Wei Lu6Department of Hepatobiliary Oncology Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Tianjin ChinaTianjin Second People's Hospital Tianjin ChinaTianjin Union Medical Center Tianjin ChinaDepartment of Hepatobiliary Oncology Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Tianjin ChinaDepartment of Hepatobiliary Oncology Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Tianjin ChinaDepartment of Hepatobiliary Oncology Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Tianjin ChinaDepartment of Hepatobiliary Oncology Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Tianjin ChinaAbstract 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.https://doi.org/10.1002/kjm2.12499epithelial–mesenchymal transitionhepatocellular carcinomamethylationmicroRNA‐424‐5ppromoter region |
| spellingShingle | Hong‐Cheng Lv Yan‐Yan Lv Gang Wang Xie‐Hua Zhang Sheng‐Nan Li Xiao‐Fen Yue Wei Lu Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells Kaohsiung Journal of Medical Sciences epithelial–mesenchymal transition hepatocellular carcinoma methylation microRNA‐424‐5p promoter region |
| title | Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells |
| title_full | Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells |
| title_fullStr | Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells |
| title_full_unstemmed | Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells |
| title_short | Mechanism of miR‐424‐5p promoter methylation in promoting epithelial–mesenchymal transition of hepatocellular carcinoma cells |
| title_sort | mechanism of mir 424 5p promoter methylation in promoting epithelial mesenchymal transition of hepatocellular carcinoma cells |
| topic | epithelial–mesenchymal transition hepatocellular carcinoma methylation microRNA‐424‐5p promoter region |
| url | https://doi.org/10.1002/kjm2.12499 |
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