Demethylation of miR-34a upregulates expression of membrane palmitoylated proteins and promotes the apoptosis of liver cancer cells
| Autor: | Ting-Yong Fan, Hao Zhang, Yu-Min Sun, Fu-Yong Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipoylation
Cell Apoptosis Caspase 3 Methylation 03 medical and health sciences 0302 clinical medicine Cell Line Tumor microRNA medicine Humans Cell Proliferation Chemistry Cell growth Liver Neoplasms Gastroenterology Membrane Proteins Cancer General Medicine Transfection Basic Study medicine.disease Demethylation Gene Expression Regulation Neoplastic MicroRNAs medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Cell apoptosis 030211 gastroenterology & hepatology Membrane palmitoylated proteins Liver cancer miR-34a |
| Zdroj: | World Journal of Gastroenterology |
| ISSN: | 1007-9327 |
| DOI: | 10.3748/wjg.v27.i6.470 |
| Popis: | Background Liver cancer is a common cancer and the main cause of cancer-related deaths worldwide. Liver cancer is the sixth most common cancer in the world. Although miR-34a and palmitoyl membrane palmitoylated protein (MPP2) are reportedly involved in various cell processes, their precise roles in liver cancer are still unclear. Aim To investigate the expression of micro RNA 34a (miR-34a), methylation of the miR-34a promoter and the expression of MPP2 in liver cancer cells and their related mechanisms. Methods Together, 78 cases of liver cancer tissues and 78 cases of adjacent tissues were collected. The methylation degree of miR-34a promoter in liver cancer/ paracancerous tissue and liver cancer cells/normal liver cells, and the expression levels of miR-34a and MPP2 in the above samples were detected. Demethylation of liver cancer cells or transfection of liver cancer cells with miR-34a mimetic was performed. The MPP2 overexpression vector was used to transfect liver cancer cells, and the changes in proliferation, invasion, apoptosis, migration, and other biological functions of liver cancer cells after the above interventions were observed. Double luciferase reporter genes were used to detect the targeting relationship between miR-34a and MPP2. Results Clinical samples showed that the expression levels of miR-34a and MPP2 in liver cancer tissues were lower than those in the normal tissues. The methylation degree of miR-34a promoter region in liver cancer cells was higher than that in normal liver cells. After miR-34a demethylation/mimetic transfection/MPP2 overexpression, the apoptosis of liver cancer cells was increased; the proliferation, invasion and migration capabilities were decreased; the expression levels of caspase 3, caspase 9, E-cadherin, and B-cell lymphoma 2 (Bcl-2)-associated X protein were increased; and the expression levels of Bcl-2, N-cadherin, and β-catenin were decreased. Double luciferase reporter genes confirmed that MPP2 is targeted by miR-34a. Rescue experiments showed that small interfering MPP2 could counteract the promoting effect of miR-34a demethylation on apoptosis and the inhibitory effect on cell proliferation, invasion, and migration. Conclusion miR-34a demethylation upregulates the expression level of MPP2 in liver cancer cells and promotes the apoptosis of liver cancer cells. miR-34a demethylation is a potential method for liver cancer treatment. |
| Databáze: | OpenAIRE |
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