Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 李力力教授 (肿瘤学系) |
| 陶谦教授 (肿瘤学系) |
| 陈家亮教授 (内科及药物治疗学系) |
| 莫树锦教授 (肿瘤学系) |
| 陈德章教授 (肿瘤学系) |
| 陈伟仪教授 (生物医学学院) |
| 杜振方先生 (肿瘤学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1038/srep26591 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/3WOS source URL
其它资讯
摘要Promoter CpG methylation is a fundamental regulatory process of gene expression. TET proteins are active CpG demethylases converting 5-methylcytosine to 5-hydroxymethylcytosine, with loss of 5 hmC as an epigenetic hallmark of cancers, indicating critical roles of TET proteins in epigenetic tumorigenesis. Through analysis of tumor methylomes, we discovered TET1 as a methylated target, and further confirmed its frequent downregulation/methylation in cell lines and primary tumors of multiple carcinomas and lymphomas, including nasopharyngeal, esophageal, gastric, colorectal, renal, breast and cervical carcinomas, as well as non-Hodgkin, Hodgkin and nasal natural killer/T-cell lymphomas, although all three TET family genes are ubiquitously expressed in normal tissues. Ectopic expression of TET1 catalytic domain suppressed colony formation and induced apoptosis of tumor cells of multiple tissue types, supporting its role as a broad bona fide tumor suppressor. Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNFhttp://aims.cuhk.edu.hk/converis/portal/Publication/382 and HOXA9. As only infrequent mutations of TET1 have been reported, compared to TET2, epigenetic silencing therefore appears to be the dominant mechanism for TET1 inactivation in cancers, which also forms a feedback loop of CpG methylation during tumorigenesis.
着者Li LL, Li C, Mao HT, Du ZF, Chan WY, Murray P, Luo B, Chan ATC, Mok TSK, Chan FKL, Ambinder RF, Tao Q
期刊名称Scientific Reports
出版年份2016
月份5
日期26
卷号6
出版社NATURE PUBLISHING GROUP
国际标準期刊号2045-2http://aims.cuhk.edu.hk/converis/portal/Publication/322
电子国际标準期刊号2045-2http://aims.cuhk.edu.hk/converis/portal/Publication/322
语言英式英语
Web of Science 学科类别Multidisciplinary Sciences; Science & Technology - Other Topics
