Biological roles of tumor-suppressor miR-34a in colon carcinogenesis

• Project/Area Number: 20590297
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• Principal Investigator: TSUCHIYA Naoto National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, 研究所, ユニット長 (30322712)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 癌 / 細胞 / 組織 / シグナル伝達 / 発現制御 / マイクロRNA / 細胞・組織

Research Abstract

miR-34a is a tumor-suppressive miRNA, which represses cancer cell proliferation by inducing cell cycle arrest. In this study, we found positive feedback activation of p53 by miR-34a through the repression of endogenous inhibitors of p53. Furthermore, a functional screening method was established to quickly and efficiently isolate tumor-suppressive miRNAs. By using this method, a novel tumor-suppressor miR-22 was successfully identified.

Research Products

• [Journal Article] Tumor-suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. (2011)
  • Author(s): Tsuchiya N, Izumiya M, Ogata-Kawata H, Okamoto K, Fujiwara Y, Nakai M, Okabe A, Schetter AJ, Bowman ED, Midorikawa Y, Sugiyama Y, Aburatani H, Harris CC, Nakagama H
  • Journal Title: Cancer Res. (in press)
• [Journal Article] NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). (2011)
  • Author(s): Wang R, Dashwood WM, Nian H, Lhr CV, Fischer KA, Tsuchiya N, Nakagama H, Ashktorab H, Dashwood RH
  • Journal Title: Int.J.Cancer. 128(11) Pages: 2581-90
• [Journal Article] NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP). (2011)
  • Author(s): Wang R
  • Journal Title: Int.J.Cancer. Volume: 128 Pages: 2581-2590
  • Peer Reviewed
• [Journal Article] MicroRNA, SND1, and alteration in translational regulation in colon carcinogenesis. (2010)
  • Author(s): Tsuchiya N, Nakagama H
  • Journal Title: Mutat.Res. 693 Pages: 94-100
• [Journal Article] Functional Screening using microRNA virus library and microarray ; a new high-throughput assay to identify tumor-suppressive microRNAs. (2010)
  • Author(s): Izumiya M, Okamoto K, Tsuchiya N, Nakagama H
  • Journal Title: Carcinogenesis 8 Pages: 1354-59
• [Journal Article] MicroRNA, SND1, and alteration in translational regulation in colon carcinogenesis. (2010)
  • Author(s): Tsuchiya N
  • Journal Title: Mutation Research Volume: 693 Pages: 94-100
  • Peer Reviewed
• [Journal Article] Functional Screening using microRNA virus library and microarray ; a new high-throughput assay to identify tumor-suppressive micro RNAs. (2010)
  • Author(s): Izumiya M
  • Journal Title: Carcinogenesis Volume: 8 Pages: 1354-1359
  • Peer Reviewed
• [Journal Article] SND1, microRNA and alterations in translational regulation in colon carcinogenesis (2010)
  • Author(s): Tsuchiya N, Nakagama H
  • Journal Title: Mutation Res. (In press)
  • Peer Reviewed
• [Journal Article] miRNA機能異常と発がん (2009)
  • Author(s): 土屋直人, 中釜斉
  • Journal Title: ゲノム医学 9 Pages: 37-41
• [Journal Article] Inhibition of peroxisome proliferator-activated receptor gamma promotes tumorigenesis through activation of the beta-catenin/T cell factor (TCF) pathway in the mouse intestine (2008)
  • Author(s): Fujisawa T, Sugiyama M, Tomimoto A, Wada K, Endo H, Takahashi H, Yoneda K, Yoneda M, Inamori M, Saito S, Terauchi Y, Kadowaki T, Tsuchiya N, Nakagama H, Nakajima A
  • Journal Title: J Pharmacol Sci. 108 Pages: 535-544
  • NAID: 130000075870
  • Peer Reviewed
• [Presentation] miR-22, a novel tumor-suppressor gene, determines p53-dependent apoptosis through repression of p21. (2011)
  • Author(s): Naoto Tsuchiya, Masashi Izumiya, Hiroko Ogata, Hitoshi Nakagama
  • Organizer: Non-coding RNA, miRNA and Cancer, Keystone Symposia
  • Place of Presentation: Banff.Canada
  • Year and Date: 2011-02-14
• [Presentation] miR-22, a novel tumor-suppressor gene, determines p53-dependent apoptosis through repression of p21. (2011)
  • Author(s): Tsuchiya N
  • Organizer: Keystone Symposia "Non-coding RNAs, miRNAs and Cancer"
  • Place of Presentation: Banff, Canada
  • Year and Date: 2011-02-14
• [Presentation] がん抑制因子miR-22による細胞運命決定機構 (2010)
  • Author(s): 土屋直人、泉谷昌志、緒方広子、中釜斉
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Activation of p53 tumor-suppressor network by microRNA-34a. (2009)
  • Author(s): 土屋直人
  • Organizer: Japan-Denmark Joint Workshop on "Molecular Cancer Research"
  • Place of Presentation: Jan.Tokyo
  • Year and Date: 2009-01-19
• [Presentation] 新規がん抑制的マイクロRNAの単離 (2009)
  • Author(s): 土屋直人
  • Organizer: 日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Activation of p53 tumor-suppressor network by microRNA-34a (2009)
  • Author(s): Naoto Tsuchiya, Hitoshi Nakagama
  • Organizer: 日本-デンマーク共同ワークショップ Molecular Cancer Research
  • Place of Presentation: 東京
• [Presentation] Molecular mechanism for the induction of senescence-like growth arrest by microRNA-34a in colon cancer cells. (2008)
  • Author(s): Naoto Tsuchiya, Masashi Izumiya, Hiroshi Tazawa, Takashi Sugimura, Hitoshi Nakagama
  • Organizer: Oligonucleotide 4th Annual Meeting of the Oligonucleotide Therapeutics Society
  • Place of Presentation: Boston
  • Year and Date: 2008-10-16
• [Presentation] MicroRNA-34a, a potential tumor suppressor, induces senescence-like growth arrest in human colon cancer cells. (2008)
  • Author(s): Naoto Tsuchiya, Hiroshi Tazawa, Masashi Izumiya, Takashi Sugimura, Hitoshi Nakagama
  • Organizer: AACR.
  • Place of Presentation: San Diego
  • Year and Date: 2008-04-13
• [Presentation] MicroRNA-34a, a potential tumor suppressor, induces senescence-like growth arrest in human colon cancer cells (2008)
  • Author(s): Naoto Tsuchiya, Hiroshi Tazawa, Masashi Izumiya, Takashi Sugimura, Hitoshi Nakagama
  • Organizer: 米国がん学会年会
  • Place of Presentation: サンディエゴ
• [Presentation] Molecular mechanism for the induction of senescence-like growth arrest by microRNA-34a in colon cancer cells (2008)
  • Author(s): Naoto Tsuchiya, Masashi Izumiya, Hiroshi Tazawa, Hitoshi Nakagama
  • Organizer: 4^<th> annual meeting of the Oligonucleotide Therapeutic Society
  • Place of Presentation: ボストン
• [Presentation] 大腸発がん過程におけるmicroRNAの役割 (2008)
  • Author(s): 土屋直人, 泉谷昌志, 中釜斉
  • Organizer: 日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 細胞傷害性ストレスに関連したmicroRNAの発現プロファイルの変化と大腸発がんとの関連性に関する解析 (2008)
  • Author(s): 落合雅子, 土屋直人, 五十嵐麻希, 益谷美都子, 杉村隆, 中釜斉
  • Organizer: 日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] ヒト大腸がんにおけるmicroRNA-34aの発現異常の検討 (2008)
  • Author(s): 泉谷昌志, 土屋直人, 落合雅子, 杉村隆, 中釜斉
  • Organizer: 日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] miR-34aによるがん抑制因子p53のフィードバック制御機構 (2008)
  • Author(s): 関千穂, 土屋直人, 杉村隆, 村上康文, 中釜斉
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] MicroRNA profiling in human fetal normal colonic mucosa and colon cancer cell lines (2008)
  • Author(s): 緒方広子, 土屋直人, 杉村隆, 中釜斉
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸
• [Book] マイクロRNAの機能スクリーニング法細胞(6月号) (2010)
  • Author(s): 泉谷昌志、土屋直人
• [Book] miR-34aによる細胞増殖抑制機構と大腸発癌における役割実験医学(5月号) (2009)
  • Author(s): 土屋直人、中釜斉
• [Book] マイクロRNAの機能異常と大腸発がんゲノム医学(2月号) (2009)
  • Author(s): 土屋直人、中釜斉
• [Book] MicroRNA実験プロトコール (2008)
  • Author(s): 監訳-河府和義, 佐々木博巳, 塩見美喜子(分担訳)
  • Total Pages: 335
  • Publisher: 羊土社
• [Book] マイクロRNAの機能異常と発がん最新医学(9月増刊号)
  • Author(s): 土屋直人
• [Patent(Industrial Property Rights)] がん抑制的マイクロRNAを含む腫瘍抑制剤 (2010)
  • Inventor(s): 中釜 斉、土屋直人、泉谷昌志、岡本康司
  • Industrial Property Rights Holder: 国立がん研究センター
  • Industrial Property Number: 2010-220275
  • Filing Date: 2010-09-30
• [Patent(Industrial Property Rights)] がん抑制的マイクロRNAを含む腫瘍抑制剤 (2010)
  • Inventor(s): 中釜斉、土屋直人、泉谷昌志、岡本康司
  • Industrial Property Rights Holder: 国立がん研究センター
  • Industrial Property Number: 2010-220275
  • Filing Date: 2010-09-30
• [Patent(Industrial Property Rights)] 大腸がん検査マーカー及び大腸がん検査方法 (2010)
  • Inventor(s): 中釜斉、土屋直人、泉谷昌志
  • Industrial Property Rights Holder: 国立がん研究センター
  • Filing Date: 2010-09-30
  • Overseas
• [Patent(Industrial Property Rights)] 大腸がん検査マーカー及び大腸がん検査方法
  • Inventor(s): 中釜斉、土屋直人、泉谷昌志
  • Industrial Property Rights Holder: 国立がん研究センター
  • Overseas