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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 676 - 686 (11page)
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Purpose Epigenetic alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. However, there are currently no standardized epigenetic biomarkers for drug sensitivity in human gastrointestinal cancer. Therefore, the aim of this study is to identify a novel epigenetic biomarker in gastrointestinal cancer.
Materials and Methods Using bisulfite sequencing and pyrosequencing analysis, DNA methylation patterns of gastric, colon primary tissues and their cancer cells were analyzed, and histone modifications were analyzed using chromatin immunoprecipitation assay. In addition, cancer cells were exposed to cisplatin and treated with a DNA methyltransferase inhibitor.
Results We report that in human gastric and colon cancers, latrophilin 2 (LPHN2) is silenced by epigenetic modifications, including CpG island methylation and aberrant histone modifications.
We also confirmed that LPHN2 was silenced by DNA hypermethylation in primary gastric and colon tumor tissues compared to their normal counterparts. Interestingly, we found that cancer cells with methylated LPHN2 showed higher sensitivity to cisplatin. Also, 5-aza- 2!-deoxycytidine combined with cisplatin decreased the cytotoxicity of cisplatin in cancer cells with methylated LPHN2. In addition, LPHN2 knockdown in cancer cells with high LPHN2 expression sensitized these cells to the anti-proliferative effects of cisplatin.
Conclusion In human gastrointestinal cancer, we found that LPHN2 is regulated by epigenetic modifications, and that cancer cells with lower LPHN2 expression show higher sensitivity to cisplatin.
Therefore, the methylation status of LPHN2 is a potential novel epigenetic biomarker for cisplatin treatment in human gastric and colon cancers.
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참고문헌 (25)
참고문헌 신청
Jones PA / 2007 / The epigenomics of cancer / Cell 128:683~692
Dawson MA / 2012 / Cancer epigenetics : from mechanism to therapy / Cell 150:12~27
Hatziapostolou M / 2011 / Epigenetic aberrations during oncogenesis / Cell Mol Life Sci 68:1681~1702
Das PM / 2004 / DNA methylation and cancer / J Clin Oncol 22:4632~4642
정규원 / 2015 / Prediction of Cancer Incidence and Mortality in Korea, 2015 / Cancer Research and Treatment 47(2):142~148
Dawson MA / 2012 / Cancer epigenetics : from mechanism to therapy / Cell 150:12~27
Hatziapostolou M / 2011 / Epigenetic aberrations during oncogenesis / Cell Mol Life Sci 68:1681~1702
Das PM / 2004 / DNA methylation and cancer / J Clin Oncol 22:4632~4642
정규원 / 2015 / Prediction of Cancer Incidence and Mortality in Korea, 2015 / Cancer Research and Treatment 47(2):142~148
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