Septin 9 hypermethylation contributes to migration and resistance to drug treatments in colon cancer
| Autor: | Xishuang Liu, Fanguo Kong, Xingyuan Diao, Jiaguo Huang, Tao Peng |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Colorectal cancer Cell growth Septin 9 Hypermethylation Colorectal cancer Drug resistance Rho A signaling fungi Pharmaceutical Science Cancer Cell migration macromolecular substances Methylation Biology medicine.disease Septin Molecular biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Apoptosis 030220 oncology & carcinogenesis DNA methylation medicine Pharmacology (medical) biological phenomena cell phenomena and immunity |
| Zdroj: | Tropical Journal of Pharmaceutical Research; Vol 16, No 4 (2017); 803-810 |
| ISSN: | 1596-9827 1596-5996 |
| DOI: | 10.4314/tjpr.v16i4.9 |
| Popis: | Purpose: To examine septin 9 gene-promoter methylation content in colorectal cancer and establish its significance in cancer progression and chemoresistance.Methods: Patient samples and colorectal cancer cell lines (CRC) were evaluated for septin 9 expression and promoter hypermethylation content. Septin 9 promoter methylation and expression in cells were perturbed by 5-AZA (5-aza-2'-deoxycytidine) treatments or overexpression and probed for changes in Rho A signaling, cell proliferation, and migration. Finally, the significance of septin 9 methylation in chemoresistance was probed using apoptotic assays in CRC cells and in a xenograft tumor model.Results: Expression analysis showed a reduction in septin 9 levels in tumor tissues (p < 0.001) and cell lines (p < 0.01), while an increase in septin 9 promoter methylation was seen, respectively ( > 2-fold; p < 0.01). Increasing septin 9 levels in CRC cells by 5-AZA treatments or overexpression showed decreased Rho A signaling and cell migration (p < 0.01), whereas cell proliferation remained unaffected. Furthermore, increasing septin 9 levels also exhibited increased cisplatin-induced apoptosis in CRC cells and reduced chemoresistance in the mouse (~2-fold; p < 0. 01).Conclusion: Septin 9 promoter hypermethylation reduces septin 9 expression and promotes migration and chemoresistance.Keywords: Septin 9, Hypermethylation, Colorectal cancer, Drug resistance, Rho A signaling |
| Databáze: | OpenAIRE |
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