Chronic inflammation-induced mimRNA functional impairment may cause inflammation-associated tumorigenesis in gastroenterological organs.

• Project/Area Number: 22390058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: OTSUKA Motoyuki 東京大学, 医学部附属病院消化器内科, 助教 (90518945)
• Co-Investigator(Kenkyū-buntansha): 立石 敬介 東京大学, 医学部附属病院消化器内科, 助教 (20396948) ; 前田 愼 横浜市立大学, 医学系研究科, 教授 (40415956)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2010: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 分子腫瘍学 / microRNA / 炎症発癌 / 炎症性発癌 / PAIP2 / レポーターマウス

Research Abstract

The novel concept “chronic impairment of microRNA function due to chronic inflammation may cause inflammation-associated tumorigenesis” was identified. Drug library screening revealed a compound which enhances microRNA function. This compound indeed had preventive effects against inflammation-associated tumorigenesis. These results may open a new strategy to prevent inflammation-associated tumorigenesis.

Research Products

• [Journal Article] Histone demethylase KDM4C regulates sphere formation by mediating the crosstalk between Wnt and Notch pathways in colonic cancer cells (2013)
  • Author(s): Otsuka M
  • Journal Title: Carcinogenesis Volume: (in press)
  • Peer Reviewed
• [Journal Article] IL28Bminor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection (2013)
  • Author(s): Otsuka M
  • Journal Title: J Gastroenterol Volume: (in press)
  • Peer Reviewed
• [Journal Article] A genome-wide association study of HCV-induced liver cirrhosis in the Japanese populationidentifies novel susceptibility loci at the MHC region (2013)
  • Author(s): Otsuka M
  • Journal Title: J Hepatol Volume: I(n press) Issue: 5 Pages: 875-882
  • DOI: 10.1016/j.jhep.2012.12.024
  • Peer Reviewed
• [Journal Article] Silencing of microRNA-122 enhances interferon- α signaling in the liver through regulating SOCS3 promoter methylation (2012)
  • Author(s): Otsuka M
  • Journal Title: Sci Rep Volume: 2 Issue: 1 Pages: 637-637
  • DOI: 10.1038/srep00637
  • Peer Reviewed
• [Journal Article] MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression (2012)
  • Author(s): Otsuka M
  • Journal Title: Hepatology Volume: 57 Issue: 1 Pages: 162
  • DOI: 10.1002/hep.26011
  • Peer Reviewed
• [Journal Article] A miRNA machinery component DDX20 controls NF-□B via microRNA-140 function (2012)
  • Author(s): Otsuka M
  • Journal Title: Biochem Biophys Res Commun Volume: 420(3) Pages: 564-9
  • Peer Reviewed
• [Journal Article] A miRNA machinery component DDX20 controls NF-κB via microRNA-140 function. (2012)
  • Author(s): Otsuka M et al. (8人中2番目)
  • Journal Title: Biochem Biophys Res Commun. Volume: 420 Issue: 3 Pages: 564-9
  • DOI: 10.1016/j.bbrc.2012.03.034
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma (2011)
  • Author(s): Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y, Matsuda K
  • Journal Title: Nat Genet Volume: 43 Pages: 455-8
  • Peer Reviewed
• [Journal Article] MicroRNA122 is a key regulator of alpha-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma (2011)
  • Author(s): Kojima K, Takata A, Vadnais C, Otsuka M, Yoshikawa T, Akanuma M, Kondo Y, Kang YJ, Kishikawa T, Kato N, Xie Z, Zhang WJ, Yoshida H,Omata M, Nepveu A, Koike K
  • Journal Title: Nat Commun Volume: 2 Pages: 338-338
  • Peer Reviewed
• [Journal Article] Receptor for activated protein kinase C : Requirement for efficient microRNA function and reduced expression in hepatocellular carcinoma (2011)
  • Author(s): Motoyuki, Otsuka
  • Journal Title: PLoS ONE Volume: 6 Issue: 9 Pages: e24359-e24359
  • DOI: 10.1371/journal.pone.0024359
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma (2011)
  • Author(s): Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y, Matsuda K
  • Journal Title: Nat Genet. Volume: 43 Issue: 5 Pages: 455-8
  • DOI: 10.1038/ng.809
  • Peer Reviewed
• [Journal Article] MicroRNA122 is a key regulator of alpha-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma (2011)
  • Author(s): Kojima K, Takata A, Vadnais C, Otsuka M, Yoshikawa T, Akanuma M, Kondo Y, Kang YJ, Kishikawa T, Kato N, Xie Z, Zhang WJ, Yoshida H, Omata M, Nepveu A, Koike K
  • Journal Title: Nat Commun. Volume: 2 Issue: 1 Pages: 338-338
  • DOI: 10.1038/ncomms1345
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. (2011)
  • Author(s): Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y. Matsuda K.
  • Journal Title: Nat Genet. Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Direct differentiation of hepatic cells from human induced plunpotent stem cells sing a limited number of cytokines. (2011)
  • Author(s): Takata A, Otsuka M, Kogiso T, Kojima K, Yoshikawa T, Tateishi R, Kato N, Shiina S, Yoshida H, Omata M, Koike K.
  • Journal Title: Hepatol Int. Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Serum Metabolomics Reveals g-Gutamyl dipeptides as Biomarkers for Discrimination among Different Forms of Liver Disease. (2011)
  • Author(s): Soga T, Suglmoto M, Monma M, Mari M, lgarashi K, Kashikura K, Ikeda S, Hirayama A, Yamsmoto T, Yoshida H, Otsuka M, Tsuji S, Yatomi Y, Sakuragawa T, Watanabe H, Nihei K, Saito T, Kawata S, Suzuki H, Tomita M, Suematsu M.
  • Journal Title: J Hepatol. Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors
  • Author(s): Otsuka M
  • Journal Title: Hepatol Int Volume: (in press)
  • Peer Reviewed
• [Presentation] Functional impairment of microRNAs induced by chronic inflammation is a cause of inflammationassociated colon tumorigenesis in mice (2013)
  • Author(s): Otsuka M
  • Organizer: The 2nd JSG International Topic Conference
  • Place of Presentation: Kagoshima
  • Year and Date: 2013-03-22
• [Presentation] Functional impairment ofmicroRNAs induced by chronic inflammation is the cause of inflammationassociated colon tumorigenesis (2013)
  • Author(s): Otsuka M
  • Organizer: JST-CREST international symposium Frontiers inImmunology & Inflammation
  • Place of Presentation: Tokyo
  • Year and Date: 2013-02-12
• [Presentation] 持続炎症に伴うmicroRNA機能異常が原因となる消化器癌の病態解明 (2011)
  • Author(s): 吉川剛史、大塚基之、小池和彦
  • Organizer: 第19回日本消化器関連学会週間
  • Place of Presentation: 福岡マリンメッセ(福岡)
  • Year and Date: 2011-10-21
• [Presentation] MicroRNA involvement inHepatocellular Carcinoma (2011)
  • Author(s): Otsuka M
  • Organizer: 日本癌学会International Symposium
  • Place of Presentation: Nagoya
  • Year and Date: 2011-10-04
• [Presentation] microRNA maychinery構成因子DDX20の発現低下に伴う microRNA機能の減弱によって惹起される肝発癌経路の同定 (2010)
  • Author(s): 大塚基之、高田朱弥、小島健太郎、前田愼、立石敬介、池上恒雄、平田善裕、建石良介、椎名秀一朗、吉田晴彦、小池和彦
  • Organizer: 臨床分子医学会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2010-04-10
• [Presentation] Functional impairment of microRNAs induced by chronic inflammation is a cause of inflammation-associated colon tumorigenesis in mice
  • Author(s): Otsuka M
  • Organizer: The 2nd JSGE International Topic Conference
  • Place of Presentation: Kagoshima
  • Invited
• [Presentation] Functional impairment of microRNAs induced by chronic inflammation is the cause of inflammation-associated colon tumorigenesis
  • Author(s): Otsuka M
  • Organizer: JST-CREST international symposium Frontiers in Immunology & Inflammation
  • Place of Presentation: Tokyo
• [Remarks]
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• [Remarks] 研究内容成果の紹介webページ
  • URL: https://sites.google.com/site/225kenncrna/
• [Remarks]
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• [Remarks]
  • URL: http://gastro.m.u-tokyo.ac.jp/med/home.html