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Combiniatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulationby ADAR1 in Gastric Cancer
  • 작성일2019-05-09
  • 최종수정일2019-05-09
  • 담당부서연구기획과
  • 연락처043-719-8033
  • 982
Digestive Diseases and Science, 2018, 63(7), 1835─1850, DOI: https://doi.org/10.1007/s10620-018-5081-9

Combiniatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulationby ADAR1 in Gastric Cancer

Charles J. Cho, Lushang Jiang; Eun Ji Lee; Dae‑Soo Kim; Byung Sik Kim; Hee Sung Kim; Hwoon‑Yong Jung; Ho‑June Song; Sung Wook Hwang; Yangsoon Park; Min Kyo Jung; Chan Gi Pack; Seung‑Jae Myung; Suhwan Chang

Abstract

    Background: Adenosine deaminase acting on RNA 1 (ADAR1) is known to mediate deamination of adenosine-to-inosine through binding to double-stranded RNA, the phenomenon known as RNA editing. Currently, the function of ADAR1 in gastric cancer is unclear.
    Aims: This study was aimed at investigating RNA editing-dependent and editing-independent functions of ADAR1 in gastric cancer, especially focusing on its influence on editing of 3′ untranslated regions (UTRs) and subsequent changes in expression of messenger RNAs (mRNAs) as well as microRNAs (miRNAs).
    Methods: RNA-sequencing and small RNA-sequencing were performed on AGS and MKN-45 cells with a stable ADAR1 knockdown. Changed frequencies of editing and mRNA and miRNA expression were then identified by bioinformatic analyses. Targets of RNA editing were further validated in patients’ samples.
    Results: In the Alu region of both gastric cell lines, editing was most commonly of the A-to-I type in 3′-UTR or intron. mRNA and protein levels of PHACTR4 increased in ADAR1 knockdown cells, because of the loss of seed sequences in 3′-UTR of PHACTR4 mRNA that are required for miRNA-196a-3p binding. Immunohistochemical analyses of tumor and paired normal samples from 16 gastric cancer patients showed that ADAR1 expression was higher in tumors than in normal tissues and inversely correlated with PHACTR4 staining. On the other hand, decreased miRNA-148a-3p expression in ADAR1 knockdown cells led to increased mRNA and protein expression of NFYA, demonstrating ADAR1’s editing-independent function.
    Conclusions: ADAR1 regulates post-tranional gene expression in gastric cancer through both RNA editing-dependent and editing-independent mechanisms.



  • 본 연구는 질병관리본부 연구개발과제(과제번호 2018-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
  • This research was supported by a fund(code 2018-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.


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