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

Research Project

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
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000)
Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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 / DNAメチル化 / ヒストン修飾
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.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (34 results)

All 2014 2013 2012 2011 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Open Access: 3 results) Presentation (12 results) (of which Invited: 1 results) Remarks (5 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 Issue: 5 Pages: e104-e104

    • DOI

      10.1038/oncsis.2014.17

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [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) Issue: 1 Pages: 31-42

    • DOI

      10.1111/hepr.12147

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitors of enhancer of zeste homologue 2 (EZH2) activate tumor suppressor microRNAs in human cancer cells.2014

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

      Oncogenesis

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic Alterations and MicroRNA Misexpression in Cancer and Autoimmune Diseases: a Critical Review.2014

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

      Clinical Reviews in Allergy & Immunology

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alterations of epigenetics and microRNAs in hepatocellular carcinoma.2014

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

      Hepatology Research

      Volume: 44 Pages: 31-42

    • Related Report
      2013 Annual Research Report
    • 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

      Volume: 47 Issue: 2 Pages: 128-135

    • DOI

      10.1007/s12016-013-8401-z

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bile Acids Increase Levels of microRNAs 221 and 222, Leading to Degradation of CDX2 During Esophageal Carcinogenesis2013

    • Author(s)
      J. Matsuzaki, H. Suzuki, H. Tsugawa, M. Watanabe, S. Hossain, T. Akaike, T. Hibi, et. al.
    • Journal Title

      Gastroenterology

      Volume: (In Press) Issue: 6 Pages: 1300-1311

    • DOI

      10.1053/j.gastro.2013.08.008

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • 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, et al.
    • Journal Title

      International Journal of Cancer

      Volume: 132 Issue: 8 Pages: 1751-1760

    • DOI

      10.1002/ijc.27862

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Annual Research Report
    • 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: 印刷中 Issue: 9 Pages: 1987-1996

    • DOI

      10.1002/jcb.24541

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • 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) Issue: 7

    • DOI

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

    • Related Report
      2013 Final Research Report
    • 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, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 426 Issue: 1 Pages: 33-37

    • DOI

      10.1016/j.bbrc.2012.08.012

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNAs in cancers and neurodegenerative disorders2012

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

      Front Genet

      Volume: 3 Pages: 194-194

    • DOI

      10.3389/fgene.2012.00194

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • 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: 186-186

    • DOI

      10.3389/fgene.2012.00186

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • 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, et al.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 11 Pages: e47396-e47396

    • DOI

      10.1371/journal.pone.0047396

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNAs in hepatobiliary and pancreatic cancers2011

    • Author(s)
      Saito Y, Suzuki H, Matsuura M, Sato A, Kasai Y, Yamada K, Saito H, Hibi T
    • Journal Title

      Frontiers in Genetics

      Volume: 2(66) Pages: 1-5

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of lansoprazole versus roxatidine on prevention of bleeding and promotion of ulcer healing after endoscopic submucosal dissection for superficial gastric neoplasia2011

    • Author(s)
      Imaeda H, Hosoe N, Suzuki H, Saito Y, Ida Y, Nakamura R, Iwao Y, Ogata H, Hibi T
    • Journal Title

      Journal of Gastroenterology

      Volume: 46 Pages: 1267-72

    • NAID

      10030294788

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of sitafloxacin-based rescue therapy for Helicobacter pylori after failure of first- and second-line therapies2011

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

      Antimicrobial Agents and Chemotherapy

      Volume: 56 Pages: 1643-5

    • Related Report
      2011 Annual Research Report
    • 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
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [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.
    • Related Report
      2013 Final Research Report
  • [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.
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] The tumor suppressor microRNA-122 is suppressed in liver cancer cells and can be reactivated by DNA methylation inhibitors.2013

    • 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
    • Related Report
      2013 Annual Research Report
  • [Presentation] MiR-1246 and miR-302 are novel targets of epigenetic therapy with DZNep and SAHA in human cancer cells.2013

    • 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
    • Related Report
      2013 Annual Research Report
  • [Presentation] NASH-肝発がんモデルにおけるマイクロRNA発現の網羅的解析と新規治療への応用2013

    • Author(s)
      高木陽子, 齋藤義正, 高杉梓, 甲浩子, 植木里美, 山田翔士, 村松俊英, 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
    • Related Report
      2013 Annual Research Report
  • [Presentation] NASH-肝発がんモデルにおけるマイクロRNA発現の網羅的解析と新規治療への応用2013

    • Author(s)
      齋藤義正、高杉 梓、齋藤英胤
    • Organizer
      第55回日本消化器病学会大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dysfunctional gastric emptying with downregulation of muscle-specific microRNAs in Helicobacter pylori-infected mice2012

    • Author(s)
      Saito Y, Suzuki H, Tsugawa H, Suzuki S, Matsuzaki J, Hirata K, Saito H, Hibi T
    • Organizer
      The 2nd Asian Pacific Topic Conference, Asian Pacific Helicobacter Pylori Meeting 2012
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Year and Date
      2012-01-14
    • Related Report
      2011 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] 発がん過程におけるエピジェネティクスとマィクロRNAの異常2011

    • Author(s)
      齋藤義正
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋(日本癌学会奨励賞受賞講演)
    • Year and Date
      2011-10-05
    • Related Report
      2011 Annual Research Report
  • [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

    • Author(s)
      齋藤義正
    • Organizer
      日本分子腫瘍マーカー研究会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
    • Invited
  • [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

    • Related Report
      2013 Final Research Report
  • [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」

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [Remarks] 慶應義塾大学薬学部研究室紹介・薬物治療学講座

    • URL

      http://www.pha.keio.ac.jp/laboratory/laboratory16.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 慶應義塾大学薬学部薬物治療学講座

    • URL

      http://www.pha.keio.ac.jp/laboratory/laboratory16.html

    • Related Report
      2012 Annual Research Report
  • [Remarks] がん研究分野の特性等を踏まえた支援活動(文部科学省科学研究費新学術領域研究)

    • URL

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

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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