연구성과물 검색 타이틀 이미지

HOME ICON HOME > Search by Achievements Type > Reports View

Reports Detailed Information
간세포암에서의 활성 산소에 의한 후성적 변화: E-cadherin 프로모터의 DNA 메틸레이션
Reports NRF is supported by Research Projects( 간세포암에서의 활성 산소에 의한 후성적 변화: E-cadherin 프로모터의 DNA 메틸레이션 | 2005 Year 신청요강 다운로드 PDF다운로드 | 임승외(서울대학교) ) data is submitted to the NRF Project Results
Researcher who has been awarded a research grant by Humanities and Social Studies Support Program of NRF has to submit an end product within 6 months(* depend on the form of business)
사업별 신청요강보기
  • Researchers have entered the information directly to the NRF of Korea research support system
Project Number C00046
Year(selected) 2005 Year
the present condition of Project 종료
State of proposition 재단승인
Completion Date 2008년 10월 29일
Year type 결과보고
Year(final report) 2008년
Research result report
  • Abstract
  • Reactive oxygen species (ROS) stress plays an important role in the progression of various tumors. DNA methylation is the most frequent epigenetic alteration in mammalian genomes, frequently mediating transcriptional repression of tumor suppressor genes in cancer cells. ROS stress and loss-of-function of tumor suppressor genes by promoter hypermethylation contribute to tumor cell invasion and metastasis. However, it remains unclear whether or how ROS trigger epigenetic changes in cancer cells. Here we demonstrate that ROS induce hypermethylation of the E-cadherin promoter through increased Snail expression. We found that Snail induces DNA methylation of the E-cadherin promoter by recruiting histone deacetylase 1 (HDAC1) and DNA methyltransferase 1 (DNMT1). In human hepatocellular carcinoma (HCC) tissues, we also observed a positive correlation among ROS stress, E-cadherin down-regulation, Snail up-regulation, and E-cadherin promoter methylation. Our data provide novel mechanistic insights into epigenetic modulations induced by ROS stress in the process of carcinogenesis. This finding is potentially relevant to the activity of ROS in silencing various tumor suppressor genes, a frequent occurrence in highly metastatic cancers.

  • Research result and Utilization method
  • In this report, we analyzed promoter regulation via Snail and methylation and identified a link between these two factors. In HCC cells, ROS induced the up-regulation of Snail expression and the methylation of the E-cadherin promoter. Specifically, Snail induced methylation of CpG sites in the E-cadherin promoter. We also investigated alterations by ROS in Snail expression and E-cadherin promoter methylation in human HCC tissue specimens. Overall, we showed that ROS induced methylation of the E-cadherin promoter via Snail.
    In conclusion, we identify a new role of ROS ? to trigger DNA methylation of tumor suppressor gene promoters in carcinogenesis. We suggest a functional pathway model of ROS-inducing epigenetic changes in which persistently elevated ROS induces CpG methylation in the E-cadherin promoter via specific recognition of an E-box by Snail. Together with human tissue data, our suggested model provides direct evidence that persistently high levels of ROS stress trigger epigenetic changes in cancer cells. This mechanism is also potentially relevant to the role of ROS in hypermethylating various tumor suppressor genes. Understanding these roles of ROS could lead to epigenetic therapy for cancer using HDAC and DNMT inhibitors in combination with various antioxidants.
  • Index terms
  • Reactive oxygen species, DNA methylation, Snail, E-cadherin, Hepatocellular carcinoma
  • List of digital content of this reports
데이터를 로딩중 입니다.
  • This document, it is necessary to display the original author and you do not have permission
    to use copyrighted material for-profit
  • In addition , it does not allow the change or secondary writings of work
데이터 이용 만족도
자료이용후 의견
트위터 페이스북
NRF Daejeon
(34113) 201, Gajeong-ro, Yuseong-gu, Daejeon, Korea
Tel: 82-42-869-6114 / Fax: 82-42-869-6777
NRF Seoul
(06792) 25, Heonreung-ro, Seocho-gu, Seoul, Korea
Tel: 82-2-3460-5500 / Fax: 82-2-3460-5759
KRM Help Center
Tel : 042-710-4360
E-mail : / Fax : 042-861-4380