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学科主题: 临床医学
题名:
Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner
作者: Wang, Jie1; Bhutani, Manisha1; Pathak, Ashutosh K.1; Lang, Wenhua1; Ren, Hening1; Jelinek, Jaroslav1; He, Rong1; Shen, Lanlan1; Issa, Jean-Pierre1; Mao, Li1
刊名: CANCER RESEARCH
发表日期: 2007-11-15
DOI: 10.1158/0008-5472.CAN-07-1337
卷: 67, 期:22, 页:10647-10652
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: DE-NOVO METHYLATION ; CELL LUNG-CANCER ; CYTOSINE-5 METHYLTRANSFERASES ; EXPRESSION ; DNMT3B ; OVEREXPRESSION ; RASSF1A ; FAMILY ; 3B
英文摘要:

DNA methyltransferase 313 (DNMT3B) is critical in de novo DNA methylation during development and tumorigenesis. We recently reported the identification of a DNMT3B subfamily, Delta DNMT3B, which contains at least seven variants, resulting from alternative pre-mRNA splicing. Delta DNMT3Bs are the predominant expression forms of DNMT3B in human lung cancer. A strong correlation was observed between the promoter methylation of RASSF1A gene but not p16 gene (both frequently inactivated by promoter methylation in lung cancer) and expression of Delta DNMT3B4 in primary lung cancer, suggesting a role of Delta DNMT3B in regulating promoterspecific methylation of common tumor suppressor genes in tumorigenesis. In this report, we provide first experimental evidence showing a direct involvement of Delta DNMT3B4 in regulating RASSF1A promoter methylation in human lung cancer cells. Knockdown of Delta DNMT3B4 expression by small interfering RNA resulted in a rapid demethylation of RASSF1A promoter and reexpression of RASSF1A mRNA but had no effect on p16 promoter in the lung cancer cells. Conversely, normal bronchial epithelial cells with stably transfected,Delta DNMT3B4 gained an increased DNA methylation in RASSF1A promoter but not p16 promoter. We conclude that promoter DNA methylation can be differentially regulated and Delta DNMT3Bs are involved in regulation of such promoterspecific de novo DNA methylation.

语种: 英语
WOS记录号: WOS:000251044000004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50411
Appears in Collections:北京大学临床肿瘤学院_肿瘤内科_期刊论文

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作者单位: 1.Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA
2.Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
3.Beijing Univ, Sch Oncol, Beijing Canc Hosp, Dept Oncol, Beijing 100871, Peoples R China

Recommended Citation:
Wang, Jie,Bhutani, Manisha,Pathak, Ashutosh K.,et al. Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner[J]. CANCER RESEARCH,2007,67(22):10647-10652.
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