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Identification and analysis of functional RNAs regulated by p53 family members in gastrointestinal tumorigenesis

Research Project

Project/Area Number 23590920
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SASAKI Yasushi  札幌医科大学, 医学部, 准教授 (70322328)

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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsp53 / p73 / p63 / 機能性RNA / miRNA / 消化器癌 / バイオマーカー
Research Abstract

The miR-200 family includes two clusters: miR-200b-200a-429 located on chromosome 1; and miR-200c-141 located on chromosome 12. We identified response elements located around both clusters that are responsive to p53 family. Here, in silico miRNA target prediction identified the v-crk sarcoma virus CT10 oncogene homolog-like (CRKL) as a potential miR-200b/200c/429 target. MiR-200b/200c/429 inhibits the expression of CRKL by directly targeting its 3'-UTR region. Importantly, CRKL expression was decreased in cancer cells with introduction of wild-type p53 and TAp63. Oncomine database shows that CRKL levels are significantly overexpressed in multiple cancer types compared with the corresponding normal tissues. We also found that CRKL was overexpressed in primary breast cancer tissues harboring mutant p53 genes. Our results indicate that a p53-inducible miRNA, 200b/200c/429 is a negative regulator of the CRKL oncoprotein and suggest a new p53-miR-200-CRKL pathway in carcinogenesis.

Report

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

    (45 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 3 results) Presentation (29 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness2014

    • Author(s)
      Tamura M, Sasaki Y, Koyama R, Takeda K, Idogawa M, Tokino T
    • Journal Title

      Oncogene

      Volume: (in press) Issue: 40 Pages: 4837-4846

    • DOI

      10.1038/onc.2013.427

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-31 expression in relation to BRAF mutation, CpG island methylation and colorectal continuum in serrated lesions2014

    • Author(s)
      Ito M, Mitsuhashi K, Igarashi H, Nosho K, Yamamoto H
    • Journal Title

      Int J Cancer

      Volume: (Epub ahead of print) Issue: 11 Pages: 2507-2515

    • DOI

      10.1002/ijc.28920

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and analysis of large intergenic non-coding RNAs regulated by p53 family members through a genome-wide analysis of p53-binding sites2014

    • Author(s)
      Idogawa M, Ohashi T, Sasaki Y, Maruyama R, Kashima L, Suzuki H, Tokino T
    • Journal Title

      Hum Mol Genet

      Volume: 23 Issue: 11 Pages: 2847-2857

    • DOI

      10.1093/hmg/ddt673

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma2014

    • Author(s)
      Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y
    • Journal Title

      Tumour Biol

      Volume: 35 Issue: 2 Pages: 973-985

    • DOI

      10.1007/s13277-013-1131-2

    • Related Report
      2013 Annual Research 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 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CHFR regulates the mitotic checkpoint by targeting PARP-1 for ubiquitination and degradation2012

    • Author(s)
      Kashima, L., Idogawa, M., Mita, H., Shitashige, M., Yamada, T., Ogi, K., Suzuki, H., Toyota, M., Ariga, H., Sasaki, Y., Tokino, T.
    • Journal Title

      J. Biol. Chem

      Volume: 287 Issue: 16 Pages: 12975-12984

    • DOI

      10.1074/jbc.m111.321828

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel approach to cancer treatment using structural hybrids of the p53 gene family.2012

    • Author(s)
      Sasaki Y, Oshima Y, Koyama R, Tamura M, Kashima L, Idogawa M, Yamashita T, Toyota M, Imai K, Shinomura Y, Tokino T.
    • Journal Title

      Cancer Gene Ther

      Volume: 19 Issue: 11 Pages: 749-56

    • DOI

      10.1038/cgt.2012.51

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heat shock enhances the expression of cytotoxic granule proteins and augments the activities of tumor-associated antigen-specific cytotoxic T lymphocytes2012

    • Author(s)
      Takahashi A, Torigoe T, Tamura Y, Kanaseki T, Tsukahara T, Sasaki Y, Kameshima H, Tsuruma T, Hirata K, Tokino T, Hirohashi Y, Sato N
    • Journal Title

      Cell Stress Chaperones

      Volume: 17 Issue: 6 Pages: 757-763

    • DOI

      10.1007/s12192-012-0348-0

    • 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 2012 Research-status 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] Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat2011

    • Author(s)
      Tanaka H, Arimura Y, Yabana T, Goto A, Hosokawa M, Nagaishi K, Yamashita K, Yamamoto H, Sasaki Y, Fujimiya M, Imai K, Shinomura Y
    • Journal Title

      J Gastr oenter ol

      Volume: 46 Issue: 2 Pages: 143-152

    • DOI

      10.1007/s00535-010-0320-7

    • NAID

      10029027000

    • 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] 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] 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 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] p53 regulates negatively the expression of the nuclear export protein XPO1, establishing a positive feedback loop2014

    • Author(s)
      Sasaki Y, Tamura M, Kobayashi T, Idogawa M, Suzuki H, Shinomura Y, Tokino T
    • Organizer
      41st Congress of the International Society of Oncology and BioMarkers
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2014-03-17
    • Related Report
      2013 Final Research Report
  • [Presentation] p53 negatively regulates the expression of the nuclear export protein XPO1, establishing a positive feedback loop2014

    • Author(s)
      Sasaki Y, Tamura M, Kobayashi T, Idogawa M, Suzuki H, Shinomura Y, Tokino T
    • Organizer
      41st Congress of the International Society of Oncology and BioMarkers
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] p53によるXPO1の抑制機構とその意義2013

    • Author(s)
      佐々木泰史, 小橋健太, 鈴木信太郎, 田村みゆき, 竹田康祐, 井戸川雅史, 篠村恭久, 時野隆至
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-05
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] p53によるXPO1の抑制機構とその意義2013

    • Author(s)
      佐々木泰史, 田村みゆき, 竹田康佑, 井戸川雅史, 丸山玲緒, 鈴木拓, 篠村恭久, 時野隆至
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness2013

    • Author(s)
      Sasaki Y, Tamura M, Koyama R, Takeda K, Idogawa M, Tokino T
    • Organizer
      6th International p63/p73 Workshop
    • Place of Presentation
      Kisarazu, Chiba, Japan
    • Year and Date
      2013-07-10
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion2013

    • Author(s)
      Sasaki Y, Koyama R, Maruyama R, Tamura M, Ohashi T, Idogawa M, Suzuki H, Shinomura Y, Tokino T
    • Organizer
      9th AACR-JCA Joint International Conference
    • Place of Presentation
      Maui, Hawaii
    • Year and Date
      2013-02-24
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] p53 によるXPO1 の抑制機構とその意義2013

    • Author(s)
      佐々木泰史,田村みゆき,竹田康佑,井戸川雅史,丸山玲緒,鈴木拓,篠村恭久,時野隆至
    • 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] Identification of novel p53 target genes by ChIP-Seq and mRNA expression analysis combined with genome-wide p53-binding motif analysis in silico2013

    • Author(s)
      Idogawa M, Ohashi T, Sasaki Y, Tokino T
    • Organizer
      9th AACR-JCA Joint International Conference
    • Place of Presentation
      Maui, Hawaii
    • Related Report
      2012 Research-status Report
  • [Presentation] Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness2013

    • Author(s)
      Tamura M, Sasaki Y, Koyama R, Yokota I, Ohashi T, Idogawa M, Tokino T
    • Organizer
      9th AACR-JCA Joint International Conference
    • Place of Presentation
      Maui, Hawaii
    • Related Report
      2012 Research-status Report
  • [Presentation] Apoptosis induction in p53-mutated cancer cells by shRNAs based on the screening of genome-wide shRNA library2013

    • Author(s)
      Ohashi T, Idogawa M, Sugisaka J, Tamura M, Yokota I, Sasaki Y, Tokino T
    • Organizer
      9th AACR-JCA Joint International Conference
    • Place of Presentation
      Maui, Hawaii
    • Related Report
      2012 Research-status Report
  • [Presentation] p53ファミリーを用いた人工ハイブリッド遺伝子の作成とアポトーシス誘導活性2012

    • Author(s)
      佐々木泰史, 大島雄一郎, 小山良太, 田村みゆき, 井戸川雅史, 篠村恭久, 時野隆至
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] p53 family network and tumor suppression2012

    • Author(s)
      佐々木泰史, 井戸川雅史, 時野隆至
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌(シンポジウム)
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] p53により発現抑制される分泌性増殖因子HDGFの同定とがん組織における発現解析2012

    • Author(s)
      佐々木泰史, 根岸秀明, 小山良太, 井戸川雅史, 鈴木拓, 今井浩三, 篠村恭久, 時野隆至
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2012-04-12
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Identification of novel p53 target genes by ChIP-Seq and mRNA expression analysis combined with genome-wide p53-binding motif analysis in silico.2012

    • Author(s)
      Idogawa M, Sasaki Y, Shinomura Y, Imai K, Tokino T
    • Organizer
      American Association of Cancer Research (AACR) annual meeting
    • Place of Presentation
      Chicago
    • Related Report
      2012 Research-status Report
  • [Presentation] p53 family network and tumor suppression2012

    • Author(s)
      佐々木泰史,井戸川雅史,時野隆至
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] ゲノム網羅的p53応答配列解析とクロマチン免疫沈降シーケンシング(ChIP-seq)を組み合わせた新規p53標的遺伝子の同定2012

    • Author(s)
      井戸川雅史,大箸智子,佐々木泰史,篠村恭久,今井浩三,時野隆至
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] p53ファミリーの新規標的FOXF1の同定と機能解析:がん細胞の浸潤・遊走能への関与2012

    • Author(s)
      田村みゆき,佐々木泰史,井戸川雅史,時野隆至
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] ゲノム網羅的shRNAライブラリースクリーニングによるp53誘導アポトーシス阻害遺伝子の同定2012

    • Author(s)
      大箸智子,井戸川雅史,佐々木泰史,時野隆至
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] p53 ファミリーを用いた人工ハイブリッド遺伝子の作成とアポトーシス誘導活性2012

    • Author(s)
      佐々木泰史,大島雄一郎,小山良太,田村みゆき,井戸川雅史,篠村恭久,時野隆至
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] hCLCA2, a p53 inducible transmembrane protein regulates cancer cell migration and invasion2011

    • Author(s)
      Sasaki Y, Koyama R, Kobayashi T, Suzuki H, Shinomura Y, Tokino T
    • Organizer
      39th Congress of the International Society of Oncology and BioMarkers
    • Place of Presentation
      Firenze, Italy
    • Year and Date
      2011-10-17
    • Related Report
      2013 Final Research Report
  • [Presentation] p53により発現抑制される分泌性増殖因子HDGFの同定がんの浸潤・遊走への関与2011

    • Author(s)
      佐々木泰史、根岸秀明、横田育子、鹿島理沙、井戸川雅史、丸山玲緒, 鈴木拓、豊田実、今井浩三、篠村恭久、時野隆至
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] がん抑制遺伝子p53研究の新展開2011

    • Author(s)
      佐々木泰史
    • Organizer
      第2回道南分子病態研究会
    • Place of Presentation
      函館
    • Year and Date
      2011-06-30
    • Related Report
      2013 Final Research Report
  • [Presentation] hCLCA2, a p53 inducible transmembrane protein regulates cancer cell migration and invasion2011

    • Author(s)
      Sasaki Y, Koyama R, Kobayashi T, Suzuki H, Shinomura Y, Tokino T
    • Organizer
      39th Congress of the International Society of Oncology and BioMarkers.
    • Place of Presentation
      Firenze, Italy
    • Related Report
      2011 Research-status Report
  • [Presentation] ゲノム網羅的shRNAライブラリースクリーニングに基づく人工miRNA /p53共発現による癌治療2011

    • Author(s)
      井戸川雅史、佐々木泰史、鹿島理沙、篠村恭久、今井浩三、時野隆至
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] p53ファミリーの新規標的遺伝子FOXF1の同定と機能解析2011

    • Author(s)
      田村みゆき,佐々木泰史、横田育子、鹿島理沙、井戸川雅史、時野隆至
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] p53ファミリーの新規標的ICAM2の同定:がん細胞の接着・遊走能への関与2011

    • Author(s)
      横田育子、佐々木泰史、田村みゆき、鹿島理沙、井戸川雅史、時野隆至
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] hCLCA2, a p53 inducible transmembrane protein regulates cancer cell migration and invasion2011

    • Author(s)
      平野雄大,佐々木泰史,小山良太,鈴木拓,杉坂淳,井戸川雅史,時野隆至
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] Apoptosis induction in cancer cells by the simultaneous transduction of p53 and artificial miRNAs based on the screening of genome-wide shRNA library2011

    • Author(s)
      杉坂淳,井戸川雅史,大箸智子,平野雄大,佐々木泰史,時野隆至
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] がん抑制遺伝子p53研究の新展開2011

    • Author(s)
      佐々木泰史
    • Organizer
      第2回 道南分子病態研究会(招待講演)
    • Place of Presentation
      函館
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://web.sapmed.ac.jp/canmol/index.html

    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] p53ファミリーキメラ分子およびその使用2012

    • Inventor(s)
      時野隆至,井戸川雅史,佐々木泰史
    • Industrial Property Rights Holder
      北海道公立大学法人 札幌医科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-08-27
    • Related Report
      2012 Research-status Report

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

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