본문으로 바로가기 주메뉴 바로가기

사용자별 맞춤메뉴

자주찾는 메뉴

추가하기
닫기

연구성과

contents area

detail content area

ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric ....
  • 작성일2021-02-22
  • 최종수정일2021-02-22
  • 담당부서연구기획과
  • 연락처043-719-8033
  • 조회수239

International Journal of Cancer, 2020.146(12), 3354-3368, DOI: https://doi.org/10.1002/ijc.32946


ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric cancer and triggers ACSL5

Seo EH, Kim HJ;Kim JH;Lim B;Park JL;Kim SY;Lee SI;Jeong HY;Song KS;Kim YS


Abstract

    Many studies have focused on global ypomethylation or hypermethylation of tumor suppressor genes, but less is known about the impact of promoter hypomethylation of oncogenes. We previously showed that promoter methylation may gradually increase or decrease during the transition from gastric mucosa (GM) to intestinal metaplasia (IM) to gastric cancer (GC). In our study, we focused on regional CpG hypomethylation of the promoter-proximal DNA of the tranion factor ONECUT2 (OC2) in IM and GC cells. We validated the hypomethylation of promoter-proximal DNA of OC2 in 160 primary GCs, in which methylation level correlated negatively with OC2 mRNA level. IM and GC cells stained positively for OC2, whereas GM cells did not. Stable transfection of OC2 in GC cells promoted colony formation, cell migration, invasion and proliferation. Moreover, OC2 knockdown with a short hairpin RNA suppressed tumorigenesis in nude mice. In addition, chromatin immunoprecipitation coupled with DNA sequencing and RNA-seq analyses revealed that OC2 triggered ACSL5, which is strongly expressed in IM of the stomach but not in GM, indicating that OC2 and ACSL5 are early-stage biomarkers for GC. We also observed a high correlation between the levels of OC2 and ACSL5 mRNAs in the GENT database These results suggest that epigenetic alteration of OC2 upregulates its expression, which then activates ACSL5; thus, OC2 is induced in IM by epigenetic alteration and triggers ACSL5 expression, and thus OC2 and ACSL5 may cooperatively promote intestinal differentiation and GC progression.



  • 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
  • This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.


본 공공저작물은 공공누리  출처표시 조건에 따라 이용할 수 있습니다 본 공공저작물은 공공누리 "출처표시" 조건에 따라 이용할 수 있습니다.
TOP