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2013 Fiscal Year Final Research Report

Identification of critical microRNAs in gastric cancer and application for epigenetic therapy.

Research Project

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Project/Area Number 23680090
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Clinical oncology
Research InstitutionKeio University

Principal Investigator

SAITO Yoshimasa  慶應義塾大学, 薬学部, 准教授 (90360114)

Project Period (FY) 2011-04-01 – 2014-03-31
Keywordsエピジェネティクス / エピジェネティック治療 / マイクロRNA / 胃がん
Research Abstract

The aim of this study is to investigate the role of microRNAs (miRNAs) during gastric carcinogenesis and the feasibility of epigenetic therapy for gastric neoplasms.MiRNA microarray analyses revealed that miR-29c was significantly down-regulated in gastric cancers and that miR-142 and miR-155 were overexpressed in gastric MALT lymphomas. MiR-1246, miR-302a and miR-4448 were up-regulated by treatment of gastric cancer cells with EZH2 inhibitors such as SAHA and DZNep. In addition, we have developed a novel miRNA promoter microarray for chromatin immunoprecipitation (ChIP)-on-chip assay. Using this custom-made miRNA promoter microarray, we have successfully performed ChIP-on-chip assay to identify miRNAs regulated by histone modification. These results indicate that misexpression of miRNAs plays critical roles during gastric carcinogenesis and that epigenetic therapy with chromatin-modifying drugs exert multiple anti-cancer effects through activation of tumor-suppressor miRNAs.

  • Research Products

    (16 results)

All 2014 2013 2012 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Inhibitors of enhancer of zeste homolog 2 (EZH2) activate tumor-suppressor microRNAs in human cancer cells2014

    • Author(s)
      Hibino S, Saito Y, Muramatsu T, Otani A, Kasai Y, Kimura M, Saito H
    • Journal Title

      Oncogenesis

      Volume: 3 Pages: e104

    • DOI

      10.1038/oncsis.2014.17

    • Peer Reviewed
  • [Journal Article] Alterations of epigenetics and microRNA in hepatocellular carcinoma2014

    • Author(s)
      Saito Y, Hibino S, Saito H
    • Journal Title

      Hepatol Res

      Volume: 44(1) Pages: 31-42

    • DOI

      10.1111/hepr.12147

    • Peer Reviewed
  • [Journal Article] Epigenetic Alterations and MicroRNA Misexpression in Cancer and Autoimmune Diseases : a Critical Review2013

    • Author(s)
      Saito Y, Saito H, Liang G, Friedman JM
    • Journal Title

      Clin Rev Allergy Immunol

    • DOI

      10.1007/s12016-013-8401-z

    • Peer Reviewed
  • [Journal Article] Bile acids increase levels of microRNAs 221 and 222, leading to degradation of CDX2 during esophageal carcinogenesis2013

    • Author(s)
      Matsuzaki J, Suzuki H, Tsugawa H, Watanabe M, Hossain S, Arai E, Saito Y, Sekine S, Akaike T, Kanai Y, Mukaisho KI, Auwerx J, Hibi T
    • Journal Title

      Gastroenterology

      Volume: 145(6) Pages: 1300-11

    • DOI

      10.1053/j.gastro.2013.08.008

    • Peer Reviewed
  • [Journal Article] The tumor suppressor microRNA-29c is downregulated and restored by celecoxib in human gastric cancer cells2013

    • Author(s)
      Saito Y, Suzuki H, Imaeda H, Matsuzaki J, Hirata K, Tsugawa H, Hibino S, Kanai Y, Saito H, Hibi T
    • Journal Title

      Int J Cancer

      Volume: 132 (8) Pages: 1751-60

    • DOI

      10.1002/ijc.27862

    • Peer Reviewed
  • [Journal Article] Suppressive Effect of the Histone Deacetylase Inhibitor, Suberoylanilide Hydroxamic Acid (SAHA), on Hepatitis C Virus Replication via Epigenetic Changes in Host Cells2013

    • Author(s)
      Sato A, Saito Y, Sugiyama K, Sakasegawa N, Muramatsu T, Fukuda S, Yoneya M, Kimura M, Ebinuma H, Hibi T, Saito H
    • Journal Title

      J Cell Biochem

      Volume: 114 (9) Pages: 1987-96

    • DOI

      10.1002/jcb.24541

    • Peer Reviewed
  • [Journal Article] Overexpression of miR-142-5p and miR-155 in gastric mucosa-associated lymphoid tissue (MALT) lymphoma resistant to Helicobacter pylori eradication2012

    • Author(s)
      Saito Y, Suzuki H, Tsugawa H, Imaeda H, Matsuzaki J, Hirata K, Hosoe N, Nakamura M, Mukai M, Saito H, Hibi T
    • Journal Title

      PLoS One

      Volume: 7(11) Pages: e47396

    • DOI

      10.1371/annotation/53d1898f-d0ae-4e5c-a585-c084a5c881bf

    • Peer Reviewed
  • [Journal Article] Development of a novel microRNA promoter microarray for ChIP-on-chip assay to identify epigenetically regulated microRNAs2012

    • Author(s)
      Saito Y, Suzuki H, Taya T, Nishizawa M, Tsugawa H, Matsuzaki J, Hirata K, Saito H, Hibi T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 426(1) Pages: 33-7

    • DOI

      10.1016/j.bbrc.2012.08.012

    • Peer Reviewed
  • [Journal Article] MicroRNAs in cancers and neurodegenerative disorders2012

    • Author(s)
      Saito Y, Saito H
    • Journal Title

      Front Genet

      Volume: 3 Pages: 194

    • DOI

      10.3389/fgene.2012.00194.eCollection2012

    • Peer Reviewed
  • [Journal Article] Role of CTCF in the regulation of microRNA expression2012

    • Author(s)
      Saito Y, Saito H
    • Journal Title

      Front Genet

      Volume: 3 Pages: 186

    • DOI

      10.3389/fgene.2012.00186.eCollection2012

    • Peer Reviewed
  • [Presentation] ヒストン修飾制御薬によるマイクロRNAを介した抗がん作用の検討2013

    • Author(s)
      日比野沙奈,齋藤義正,村松俊英,大谷亜希,笠井雄祐,植木里美,山田翔士,木村真規,齋藤英胤
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      20131000
  • [Presentation] MiR-1246 and miR-302 are novel targets of epigenetic therapy with DZNep and SAHA in human cancer cells2013

    • Author(s)
      Hibino S, Saito Y, Muramatsu T, Otani A, Kasai Y, Kimura M, Saito H
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      Orlando, FL.
    • Year and Date
      20130500
  • [Presentation] The tumor suppressor microRNA-122 is suppressed in liver cancer cells and can be reactivated by DNA methylation inhibitors2013

    • Author(s)
      Matsuura M, Saito Y, Doke Y, Yoshida T, Genka A, Muramatsu T, Kimura M, Arai E, Kanai Y, Saito H
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      Orlando, FL.
    • Year and Date
      20130500
  • [Presentation] がん細胞に対するDZNepおよびSAHAの投与によるマイクロRNA発現変化の網羅的検討2013

    • Author(s)
      日比野沙奈,齋藤義正,村松俊英,大谷亜希,笠井雄祐,植木里美,山田翔士,木村真規,齋藤英胤
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      20130300
  • [Presentation] がんに対するエピジェネティック治療によるマイクロRNA発現変化の網羅的解析2012

    • Author(s)
      齋藤義正,村松俊英,木村真規,齋藤英胤
    • Organizer
      日本分子腫瘍マーカー研究会
    • Place of Presentation
      札幌
    • Year and Date
      20120900
  • [Remarks] 文部科学省科学研究費新学術領域研究「がん研究分野の特性等を踏まえた支援活動」 にて当該研究の紹介を行っている。

    • URL

      http://ganshien.umin.jp/public/research/main/saito/index.html

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Published: 2015-07-16  

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