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Original Research Article | OPEN ACCESS

Septin 9 hypermethylation contributes to migration and resistance to drug treatments in colon cancer

Tao Peng1,2, Fanguo Kong2, Xingyuan Diao2, Jiaguo Huang2, Xishuang Liu1

1Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000; 2Department of Gastroenterology, The People’s Hospital of Laiwu City, Laiwu, Shangdong, 271199, China.

For correspondence:-  Xishuang Liu   Email: xishuangliu@hotmail.com   Tel:+8653282911219

Received: 15 December 2016        Accepted: 17 March 2017        Published: 30 April 2017

Citation: Peng T, Kong F, Diao X, Huang J, Liu X. Septin 9 hypermethylation contributes to migration and resistance to drug treatments in colon cancer. Trop J Pharm Res 2017; 16(4):803-810 doi: 10.4314/tjpr.v16i4.9

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

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

Impact Factor
Thompson Reuters (ISI): 0.6 (2023)
H-5 index (Google Scholar): 49 (2023)

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