Identification of the Warburg effect-associated microRNAs and those targeting genes and clinical application of those

• Project/Area Number: 15K10120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka Medical College
• Principal Investigator: UCHIYAMA Kazuhisa 大阪医科大学, 医学部, 教授 (80232867)
• Co-Investigator(Kenkyū-buntansha): 赤尾 幸博 岐阜大学, 大学院連合創薬医療情報研究科, 教授 (00222505)
• Research Collaborator: TANIGUCHI Kohei 大阪医科大学, 医学部, 助教 (70779686)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: microRNA / Warburg 効果 / PTBP1 / RNA helicase / MYC / Warburg効果

Outline of Final Research Achievements

In this project, we found that cancer-specific energy metabolism (Warburg effect) is regulated by several organ-specific microRNAs (miRNAs). Especially, MIR122, 137 and 206 had organ specificity and regulated Warburg effect-associated genes, i.e., PKM or PTBP1. Also, we indicated that PTBP1 is novel oncogene in colorectal tumors and that up-regulation of PTBP1 was induced by dysregulation of the MIR1 and 133b. Moreover, we partially clarified the functions of the Warburg effect-associated genes in chemo-resistant cancer cells. Namely, PKM2 was dominant in cancer cells, but in chemo-resistant cancer cells, PKM1 was re-up-regulated through the reverse shift of PKM isoforms.

Research Products

• [Journal Article] Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells. (2018)
  • Author(s): Taniguchi K, Iwatsuki A, Sugito N, Shinohara H, Kuranaga Y, Oshikawa Y, Tajirika T, Futamura M, Yoshida K, Uchiyama K, Akao Y.
  • Journal Title: Molecular Carcinogenesis Volume: 57(5) Issue: 5 Pages: 579-589
  • DOI: 10.1002/mc.22781
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Organ-Specific MicroRNAs (MIR122, 137, and 206) Contribute to Tissue Characteristics and Carcinogenesis by Regulating Pyruvate Kinase M1/2 (PKM) Expression. (2018)
  • Author(s): Taniguchi K, Sugito N, Shinohara H, Kuranaga Y, Inomata Y, Komura K, Uchiyama K, Akao Y.
  • Journal Title: International Journal of Molecular Sciences Volume: 19(5) Issue: 5 Pages: 1276-1276
  • DOI: 10.3390/ijms19051276
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors. (2016)
  • Author(s): Taniguchi K, Sakai M, Sugito N, Kumazaki M, Shinohara H, Yamada N, Nakayama T, Ueda H, Nakagawa Y, Ito Y, Futamura M, Uno B, Otsuki Y, Yoshida K, Uchiyama K, Akao Y.
  • Journal Title: Oncotarget Volume: 0000 Issue: 14 Pages: 0000-0000
  • DOI: 10.18632/oncotarget.8005
  • Peer Reviewed / Open Access
• [Journal Article] PKM1 is involved in resistance to anti-cancer drugs. (2016)
  • Author(s): Taniguchi K, Sakai M, Sugito N, Kuranaga Y, Kumazaki M, Shinohara H, Ueda H, Futamura M, Yoshida K, Uchiyama K, Akao Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 0000 Issue: 1 Pages: 0000-0000
  • DOI: 10.1016/j.bbrc.2016.03.074
  • Peer Reviewed
• [Journal Article] Positive feedback of DDX6/c-Myc/PTB1 regulated by miR-124 contributes to maintenance of the Warburg effect in colon cancer cells. (2015)
  • Author(s): Taniguchi K, Sugito N, Kumazaki M, Shinohara H, Yamada N, Matsuhashi N, Futamura M, Ito Y, Otsuki Y, Yoshida K, Uchiyama K, Akao Y.
  • Journal Title: Biochim Biophys Acta. Volume: 9 Issue: 9 Pages: 1971-80
  • DOI: 10.1016/j.bbadis.2015.06.022
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms. (2015)
  • Author(s): Taniguchi K, Ito Y, Sugito N, Kumazaki M, Shinohara H, Yamada N, Nakagawa Y, Sugiyama T, Futamura M, Otsuki Y, Yoshida K, Uchiyama K, Akao Y.
  • Journal Title: Sci Rep. Volume: 2 Issue: 1 Pages: 8647-8647
  • DOI: 10.1038/srep08647
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer. (2015)
  • Author(s): Taniguchi K, Sugito N, Kumazaki M, Shinohara H, Yamada N, Nakagawa Y, Ito Y, Otsuki Y, Uno B, Uchiyama K, Akao Y.
  • Journal Title: Cancer Lett. Volume: 1 Issue: 1 Pages: 17-27
  • DOI: 10.1016/j.canlet.2015.03.026
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] MicroRNAの臓器特異性と新規がん遺伝子PTBP１の機能解析 (2018)
  • Author(s): 谷口高平、赤尾幸博、内山和久
  • Organizer: 第51回 制癌剤適応研究会
• [Presentation] Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells (2017)
  • Author(s): 谷口高平、杉戸信彦、田尻下敏弘、二村学、吉田和弘、内山和久、赤尾幸博
  • Organizer: 第76回 日本癌学会学術総会
• [Presentation] がん特異的代謝におけるmiR-34aの機能解析 (2017)
  • Author(s): 谷口高平、杉戸信彦、赤尾幸博、内山和久
  • Organizer: 第21回 日本がん分子標的治療学会学術集会
• [Presentation] がん特異的エネルギー代謝を標的としたRNA創薬 (2016)
  • Author(s): 谷口高平, 高井朋聡, 吉川勇希, 杉戸信彦, 内山和久, 東治人, 赤尾幸博
  • Organizer: 日本核酸医薬学会 第2回年会
  • Place of Presentation: 東京理科大学葛飾キャンパス図書館大ホール
  • Year and Date: 2016-11-15
• [Presentation] Pyruvate kinase isoforms are dysregulated by organ-specific microRNA in cancer development. (2016)
  • Author(s): 谷口高平, 杉戸信彦, 内山和久, 赤尾幸博
  • Organizer: 第75回, 日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 新規重要がん遺伝子PTBP1の機能及び発現調節機構の解析 (2016)
  • Author(s): 谷口高平,内山和久,赤尾幸博
  • Organizer: 第４回 がんと代謝研究会
  • Place of Presentation: 鹿児島県民交流センター
  • Year and Date: 2016-07-07
• [Presentation] 新規がん遺伝子PTBP1の機能及び発現調節機構の解析 (2016)
  • Author(s): 谷口高平、杉戸信彦、倉永祐希、熊崎実南、篠原悠、内山和久、赤尾幸博
  • Organizer: 日本がん分子標的治療学会
  • Place of Presentation: 別府国際コンベンションセンター、別府市、大分県
  • Year and Date: 2016-05-31
• [Remarks]
  • URL: https://www.osaka-med.ac.jp/deps/sur/html/laboratory.html