Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 吴兆文教授 (外科学系) |
| 梁荣华博士 (外科学系) |
| 杜健华教授 (药剂学院) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1002/mc.22508 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/0WOS source URL
Scopushttp://aims.cuhk.edu.hk/converis/portal/Publication/0Scopus source URL
其它资讯
摘要Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. The majority of studies to date focused on genetic mutations and epigenetic changes that drive the CRC carcinogenesis process. Xenobiotic transporters play an important role in safeguarding our body from external toxic substances. These transporters lining the gastrointestinal tract protect us from dietary carcinogens. This study aimed to investigate the downregulation of an efflux transporter ABCG2 in CRC versus normal colon mucosa, so as to shed light on its relevance to CRC initiation and progression. We found that ABCG2 expression is at least 5http://aims.cuhk.edu.hk/converis/portal/Publication/0-fold lower in adenomatous polyps and colon carcinoma specimens obtained from CRC patients than in their matched pair of adjacent normal colon mucosa. The underlying mechanism(s) for ABCG2 under-expression in CRC is currently not known. To this end, aberrant promoter methylation of ABCG2 has been reported to cause its repression in a few cancer types including renal carcinoma and multiple myeloma. In this study, miR-2http://aims.cuhk.edu.hk/converis/portal/Publication/03 was found to be downregulated in all polyps and CRC specimens, relative to adjacent normal colon mucosa. We demonstrated that the de novo DNA methyltransferase DNMT3b is a direct target of miR-2http://aims.cuhk.edu.hk/converis/portal/Publication/03. Importantly, by relieving the repression on DNMT3b, the lower expression of miR-2http://aims.cuhk.edu.hk/converis/portal/Publication/03 in CRC caused ABCG2 promoter methylation and remarkable lower ABCG2 expression in colon cancer cell lines and the patient CRC specimens. The restoration of ABCG2 function via modulating this new microRNA-methylation mechanism in precancerous cells may represent an attractive strategy to delay the carcinogenesis process. ? 2http://aims.cuhk.edu.hk/converis/portal/Publication/016 Wiley Periodicals, Inc.
着者To K.K.W., Leung W.W., Ng S.S.M.
期刊名称Molecular Carcinogenesis
详细描述doi:1http://aims.cuhk.edu.hk/converis/portal/Publication/0.1http://aims.cuhk.edu.hk/converis/portal/Publication/0http://aims.cuhk.edu.hk/converis/portal/Publication/02/mc.225http://aims.cuhk.edu.hk/converis/portal/Publication/08.
出版年份2http://aims.cuhk.edu.hk/converis/portal/Publication/017
月份2
日期1
卷号56
期次2
出版社John Wiley & Sons Inc.
出版地United States
页次464 - 477
国际标準期刊号http://aims.cuhk.edu.hk/converis/portal/Publication/0899-1987
电子国际标準期刊号1http://aims.cuhk.edu.hk/converis/portal/Publication/098-2744
语言英式英语
关键词ABCG2, carcinogenesis, colorectal cancer, DNA methylation, microRNA
