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Analysis of epigenome and functional RNA in colorectal cancer cells and cancer stem cells

Research Project

Project/Area Number 23501261
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Carcinogenesis
Research InstitutionSapporo Medical University

Principal Investigator

SUZUKI Hiromu  札幌医科大学, 医学部, 教授 (20381254)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords大腸癌 / 癌幹細胞 / エピジェネティクス / DNAメチル化 / microRNA / メチル化 / noncoding RNA
Research Abstract

By analyzing epigenome and microRNA expression profiling in colorectal cancer (CRC) cells, we identified a series of epigenetically silenced microRNA genes. We found that DNA methyltransferase 1 (DNMT1) is essential for the maintenance of cancer stem-like cells (CSC)/ cancer initiating cells (CIC), and we also identified microRNA genes which are differentially expressed in CSC/CIC. We carried out genome and epigenome analysis in precursor and malignant lesions in colorectum, and identified aberrant DNA methylation patterns in the premalignant stage. Finally, by performing integrative analysis of molecular, pathological and endoscopic findings of premalignant colorectal lesions, we identified a novel surface microstructure which is specific to the precursor lesions of CpG island methylator phenotype (CIMP)-positive CRC.

Report

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

    (49 results)

All 2014 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (28 results) (of which Invited: 2 results)

  • [Journal Article] Colorectal carcinomas with CpG island methylator phenotype 1 frequently contain mutations in chromatin regulators2014

    • Author(s)
      Tahara T, Yamamoto E, Madireddi P, Suzuki H, Maruyama R, Chung W, Garriga J, Jelinek J, Yamano HO, Sugai T, Kondo Y, Toyota M, Issa JP, Estecio MR
    • Journal Title

      Gastroenterology

      Volume: 146 Issue: 5 Pages: 530-538

    • DOI

      10.1158/0008-5472.can-13-1865

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of microRNA-31 with BRAF mutation, colorectal cancer survival, and serrated pathway2014

    • Author(s)
      Nosho K (他18名), Igarashi H, Ito M, Nojima M, Yamamoto H, Shinomura Y
    • Journal Title

      Carcinogenesis

      Volume: 35 Issue: 4 Pages: 776-783

    • DOI

      10.1093/carcin/bgt374

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA methyltransferase 1 is essential for initiation of the colon cancers2013

    • Author(s)
      Morita R,Hirohashi Y,Suzuki H, et al
    • Journal Title

      Experimental and Molecular Pathology

      Volume: 94 Issue: 2 Pages: 322-329

    • DOI

      10.1016/j.yexmp.2012.10.004

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methylation of a panel of microRNA genes is a novel biomarker for detection of bladder cancer2013

    • Author(s)
      Shimizu T, Suzuki H, Nojima M, Kitamura H, Yamamoto E, Maruyama R, Ashida M, Hatahira T, Kai M, Masumori N, Tokino T, Imai K, Tsukamoto T, Toyota M
    • Journal Title

      Eur Urol

      Volume: 63 Issue: 6 Pages: 1091-1100

    • DOI

      10.1016/j.eururo.2012.11.030

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization.2013

    • Author(s)
      Sawada T, Yamamoto E, Suzuki H
    • Journal Title

      Genes Chromosomes Cancer

      Volume: 52(2) Issue: 2 Pages: 140-9

    • DOI

      10.1002/gcc.22013

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneous rupture of an advanced pancreatoblastoma : aberrant RASSF1A methylation and CTNNB1 mutation as molecular genetic markers2013

    • Author(s)
      Honda S, Okada T, Miyagi H, Minato M, Suzuki H, Taketomi A
    • Journal Title

      J Pediatr Surg

      Volume: 48 Issue: 4 Pages: e29-e32

    • DOI

      10.1016/j.jpedsurg.2013.02.038

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] AKR1B10, a transcriptional target of p53, is Downregulated in Colorectal Cancers Associated with Poor Prognosis2013

    • Author(s)
      Ohashi T et al.
    • Journal Title

      Mol Cancer Res

      Volume: 11 Issue: 12 Pages: 1554-1163

    • DOI

      10.1158/1541-7786.mcr-13-0330-t

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors2012

    • Author(s)
      Takeshi Niinuma
    • Journal Title

      Cancer research

      Volume: 72 Issue: 5 Pages: 1126-36

    • DOI

      10.1158/0008-5472.can-11-1803

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel pit pattern identifies the precursor of colorectal cancer derived from sessile serrated adenoma.2012

    • Author(s)
      Kimura T, Yamamoto E, Yamano HO.
    • Journal Title

      Am J Gastroenterol.

      Volume: 107(3) Issue: 3 Pages: 460-9

    • DOI

      10.1038/ajg.2011.457

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA methylation and microRNA dysregulation in cancer.2012

    • Author(s)
      Suzuki Hiromu
    • Journal Title

      Mol Oncol

      Volume: 6 Issue: 6 Pages: 567-78

    • DOI

      10.1016/j.molonc.2012.07.007

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Emerging links between epigenetic alterations and dysregulation of noncoding RNAs in cancer2012

    • Author(s)
      Maruyama R, Suzuki H, Yamamoto E, Imai K, Shinomura Y
    • Journal Title

      Tumour Biol

      Volume: 33 Issue: 2 Pages: 277-85

    • DOI

      10.1007/s13277-011-0308-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant Methylation of RASGRF1 Is Associated with an Epigenetic Field Defect and Increased Risk of Gastric Cancer.2012

    • Author(s)
      Takamaru H, Yamamoto E, Suzuki H.
    • Journal Title

      Cancer Prev Res (Phila)

      Volume: 5(10) Issue: 10 Pages: 2012-2012

    • DOI

      10.1158/1940-6207.capr-12-0056

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma2012

    • Author(s)
      Aoki Y, Nojima M, Suzuki H, Yasui H, Maruyama R, Yamamoto E, Ashida M, Itagaki M, Asaoku H, Ikeda H, Hayashi T, Imai K, Mori M, Tokino T, Ishida T, Toyota M, Shinomura Y
    • Journal Title

      Genome Med

      Volume: 4 Pages: 101-101

    • URL

      http://genomemedicine.com/content/4/12/101

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Dissection of Premalignant Colorectal Lesions Reveals Early Onset of the CpG Island Methylator Phenotype.2012

    • Author(s)
      Yamamoto E, Suzuki H, Yamano HO
    • Journal Title

      Am J Pathol

      Volume: 181(5) Issue: 5 Pages: 1847-61

    • DOI

      10.1016/j.ajpath.2012.08.007

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion2012

    • Author(s)
      Sasaki Y, Sugisaka J, Maruyama R, Sugisaka J, Tamura M, Sugisaka J, Suzuki H, Idogawa M, Shinomura Y, Tokino T
    • Journal Title

      Cancer Biol Ther

      Volume: 13 Issue: 14 Pages: 1512-1521

    • DOI

      10.4161/cbt.22280

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide analysis of DNA methylation identifies novel cancer-related genes in hepatocellular carcinoma2012

    • Author(s)
      Shitani M, Sasaki S, Akutsu N, Takagi H, Suzuki H, Nojima M, Yamamoto H, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y
    • Journal Title

      Tumour Biol

      Volume: 33 Issue: 5 Pages: 1307-1317

    • DOI

      10.1007/s13277-012-0378-3

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant DNA methylation associated with aggressiveness of gastrointestinal stromal tumour2012

    • Author(s)
      Okamoto Y
    • Journal Title

      Gut

      Volume: 61 Issue: 3 Pages: 392-401

    • DOI

      10.1136/gut.2011.241034

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer2011

    • Author(s)
      Suzuki H
    • Journal Title

      Cancer Res

      Volume: 71 Issue: 17 Pages: 5646-5658

    • DOI

      10.1158/0008-5472.can-11-1076

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors2011

    • Author(s)
      Seiko Kamimae
    • Journal Title

      Cancer prevention research

      Volume: 4 Issue: 5 Pages: 674-83

    • DOI

      10.1158/1940-6207.capr-10-0214

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological and molecular features of colorectal serrated neoplasias with different mucosal crypt patterns2011

    • Author(s)
      Yano Y, Konishi K, Yamochi T, Katagiri A, Nozawa H, Suzuki H, Toyota M, Kubota Y, Muramoto T, Kobayashi Y, Tojo M, Konda K, Makino R, Kaneko K, Yoshikawa N, Ota H, Imawari M
    • Journal Title

      Am J Gastroenterol

      Volume: 106 Issue: 7 Pages: 1351-1358

    • DOI

      10.1038/ajg.2011.76

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] p53 negatively regulates the hepatoma growth factor HDGF2011

    • Author(s)
      Sasaki Y, Negishi H, Idogawa M, Yokota I, Koyama R, Kusano M, Suzuki H, Fujita M, Maruyama R, Toyota M, Saito T, Tokino T
    • Journal Title

      Cancer Res

      Volume: 71 Issue: 22 Pages: 7038-47

    • DOI

      10.1158/0008-5472.can-11-1053

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 腸管洗浄液のメチル化検出による大腸癌診断法の開発2013

    • Author(s)
      原田拓,山本英一郎,野島正寛,丸山玲緒,佐藤亜紀子,甲斐正広,山野泰穂,鈴木拓
    • Organizer
      第33回日本分子腫瘍マーカー研究会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-02
    • Related Report
      2013 Final Research Report
  • [Presentation] 消化器癌の発生や進展に関与する長鎖ncRNA の量的・質的異常の探索と臨床応用への試み2013

    • Author(s)
      丸山玲緒,山本英一郎,粂川昂平,津矢田明泰,鈴木亮,芦田仁己,甲斐正広,佐藤亜紀子,新沼猛,山野泰穂,菅井有,篠村恭久,時野隆至,鈴木拓
    • Organizer
      第33回日本分子腫瘍マーカー研究会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-02
    • Related Report
      2013 Final Research Report
  • [Presentation] がんエピゲノム解析による病態解明と診断応用2013

    • Author(s)
      鈴木拓
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] マイクロRNA 遺伝子のエピジェネティクス異常と臨床応用2013

    • Author(s)
      鈴木拓,山本英一郎,丸山玲緒,鈴木 亮,清水崇,原田拓,山野泰穂,野島正寛,高塚伸太朗,新沼猛、甲斐正広,篠村恭久,今井浩三
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 消化器癌において重要な役割を果たす長鎖ncRNA の網羅的同定の試み2013

    • Author(s)
      丸山玲緒,山本英一郎,粂川昂平,津矢田明泰,鈴木亮,芦田仁己,佐藤亜紀子,甲斐正広,山野泰穂,菅井有,篠村恭久,時野隆至,鈴木拓
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] マイクロRNA遺伝子のエピジェネティクス異常と臨床応用2013

    • Author(s)
      鈴木 拓
    • 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] microRNA遺伝子のメチル化を用いた膀胱癌新規バイオマーカーの開発2013

    • Author(s)
      鈴木 拓
    • Organizer
      第64回日本電気泳動学会総会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] Epigenetic silencing of neurotensin receptor type 1 (NTSR1) in colorectal tumor2013

    • Author(s)
      Hiromu Suzuki
    • Organizer
      AACR International Conference on Frontiers in Basic Cancer Research
    • Place of Presentation
      National Harbor, MD, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 大腸腫瘍におけるニューロテンシン受容体1型遺伝子のメチル化と臨床的意義2013

    • Author(s)
      鈴木 拓
    • Organizer
      第9回日本消化管学会総会学術総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 消化管腫瘍のエピゲノムおよびnon-coding RNA 解析による分子マーカー探索2012

    • Author(s)
      鈴木拓
    • Organizer
      第32回日本分子腫瘍マーカー研究会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-18
    • Related Report
      2013 Final Research Report
  • [Presentation] microRNA-196a とHOTAIRの過剰発現は消化管間質腫瘍の悪性度と相関する2012

    • Author(s)
      鈴木拓,新沼猛,野島正寛,丸山玲緒,山本英一郎,甲斐正広,能正勝彦,山本博幸,時野隆至,今井浩三,篠村恭久
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 大腸癌においてエピジェネティックに抑制されている長鎖ncRNA の網羅的同定の試み2012

    • Author(s)
      丸山玲緒,粂川昇平,山本英一郎,井戸川雅史,野島正寛,甲斐正広,能正勝彦,佐々木泰史,山野泰穂,菅井有,篠村恭久,時野隆至,鈴木拓
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 大腸腫瘍におけるニューロテンシン受容体1 型遺伝子のメチル化と臨床的意義2012

    • Author(s)
      山本英一郎,鈴木拓,神前正幸,丸山玲緒,山野泰穂,澤田武,能正勝彦,山本博幸,甲斐正広,時野隆至,菅井有,今井浩三,篠村恭久
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 大腸腫瘍におけるニューロテンシン受容体1 型遺伝子のメチル化と臨床的意義2012

    • Author(s)
      鈴木拓,山本英一郎,丸山玲緒,山野泰穂,甲斐正広,山本博幸,篠村恭久
    • Organizer
      第23回日本消化器癌発生学会総会
    • Place of Presentation
      徳島
    • Related Report
      2013 Final Research Report
  • [Presentation] miR-196aおよびHOTAIR の過剰発現は消化管間質腫瘍の悪性度を促進する2012

    • Author(s)
      鈴木拓,野島正寛,丸山玲緒,山本英一郎,津矢田明泰,篠村恭久
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumor2012

    • Author(s)
      鈴木 拓
    • Organizer
      第71回日本癌学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 大腸腫瘍におけるニューロテンシン受容体1型遺伝子のメチル化と臨床的意義2012

    • Author(s)
      鈴木 拓
    • Organizer
      第20回日本消化器病関連学会週間(JDDW)
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] 大腸腫瘍におけるニューロテンシン受容体1型遺伝子のメチル化と臨床的意義2012

    • Author(s)
      鈴木 拓
    • Organizer
      第23回日本消化器癌発生学会総会
    • Place of Presentation
      徳島
    • Related Report
      2012 Research-status Report
  • [Presentation] 大腸がんのエピゲノム解析によるがん関連miRNA遺伝子の同定2012

    • Author(s)
      鈴木 拓
    • Organizer
      日本食品化学工学学会第59回大会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 大腸癌のエピゲノム解析による癌関連miRNA 遺伝子の同定2011

    • Author(s)
      鈴木拓,山本英一郎,丸山玲緒,篠村恭久,今井浩三,豊田実
    • Organizer
      第31回日本分子腫瘍マーカー研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-02
    • Related Report
      2013 Final Research Report
  • [Presentation] 消化管癌におけるmicroRNA 遺伝子のエピジェネティックな不活化の網羅的解析2011

    • Author(s)
      鈴木拓,山本英一郎,篠村恭久
    • Organizer
      第97回日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] エピゲノム解析による造血器腫瘍の新たな分子標的の同定2011

    • Author(s)
      豊田実,野島正寛,鈴木拓,丸山玲緒,山本英一郎,甲斐正広,時野隆至,篠村恭久,今井浩三
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 大腸癌のエピゲノム解析からアプローチする癌関連miRNA の探索2011

    • Author(s)
      鈴木拓,山本英一郎,野島正寛,丸山玲緒,高丸博之,甲斐正広,時野隆至,今井浩三,豊田実,篠村恭久
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 大腸癌におけるmicroRNA 遺伝子のエピジェネティックな制御の網羅的解析2011

    • Author(s)
      鈴木拓,山本英一郎,丸山玲緒,野島正寛,今井浩三,篠村恭久,豊田実
    • Organizer
      第22回日本消化器癌発生学会総会
    • Place of Presentation
      佐賀
    • Related Report
      2013 Final Research Report
  • [Presentation] microRNA遺伝子のエピジェネティクス異常によるがん診断

    • Author(s)
      鈴木 拓
    • Organizer
      日本がん分子標的治療学会第9回トランスレーショナルリサーチワークショップ
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 大腸癌におけるmiRNA遺伝子のエピジェネティックな制御の解析

    • Author(s)
      鈴木 拓
    • Organizer
      第5回日本エピジェネティクス研究会年会
    • Place of Presentation
      熊本
    • Related Report
      2011 Research-status Report
  • [Presentation] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer

    • Author(s)
      鈴木 拓
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] The origin of colorectal cancer with CpG island methylator phenotype

    • Author(s)
      鈴木 拓
    • Organizer
      International Society of Oncology and Biomarker (ISOBM) 2011
    • Place of Presentation
      イタリア・フィレンツェ
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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