Development of strategy to design anticancer drug based on ceRNA network

• Project/Area Number: 18KT0016
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: The University of Tokyo
• Principal Investigator: Nobuyoshi Akimitsu 東京大学, アイソトープ総合センター, 教授 (40294962)
• Co-Investigator(Kenkyū-buntansha): 浜田 道昭 早稲田大学, 理工学術院, 教授 (00596538)
• Project Period (FY): 2018-07-18 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2020: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2019: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: RNA / ネットワーク

Outline of Final Research Achievements

The post-transcriptional gene regulation is achieved by RNA-based gene regulatory networks. The RNA-based networks are classified by RNA-RNA and RNA-protein network. In this study, we investigate these RNA-based network to reveal gene regulation of cancer and we aimed development of new strategy to develop anticancer drugs. Our study has revealed that RNA-protein network is remodeled in response to chronic hypoxia and we found the target molecules of RNA-protein network under hypoxia.

Academic Significance and Societal Importance of the Research Achievements

慢性的低酸素に対してがん細胞が適応的に応答するために遺伝子発現パターンが変化するが、この遺伝子発現を調節するためのRNA-タンパク質ネットワークを明らかにし、そのうで、このネットワーク制御を担うたんぱく質を多数同定した。本研究で同定したタンパク質のなかには、すでにがん増殖やがん転移に関与することが報告されているタンパク質も存在した。この結果は、我々の研究アプローチによって、がん増殖やがん転移を担う責任分子を効率的に特定できること、すなわち、有望な抗がん剤標的分子を効率的に特定できることを示している。本研究成果はがん細胞の慢性的低酸素適応を標的とした新しい抗がん剤開発に貢献する。

Research Products

• [Journal Article] RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival (2022)
  • Author(s): Taniue Kenzui、Tanu Tanzina、Shimoura Yuki、Mitsutomi Shuhei、Han Han、Kakisaka Rika、Ono Yusuke、Tamamura Nobue、Takahashi Kenji、Wada Youichiro、Mizukami Yusuke、Akimitsu Nobuyoshi
  • Journal Title: International Journal of Molecular Sciences Volume: 23 Issue: 1 Pages: 496-496
  • DOI: 10.3390/ijms23010496
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] hnRNPH1-MTR4 complex-mediated regulation of <i>NEAT1v2</i> stability is critical for <i>IL8</i> expression (2021)
  • Author(s): Tanu Tanzina、Taniue Kenzui、Imamura Katsutoshi、Onoguchi-Mizutani Rena、Han Han、Jensen Torben Heick、Akimitsu Nobuyoshi
  • Journal Title: RNA Biology Volume: 18 Issue: sup1 Pages: 537-547
  • DOI: 10.1080/15476286.2021.1971439
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of micropeptides in biology (2021)
  • Author(s): Vitorino Rui、Guedes Sofia、Amado Francisco、Santos Manuel、Akimitsu Nobuyoshi
  • Journal Title: Cellular and Molecular Life Sciences Volume: 78 Issue: 7 Pages: 3285-3298
  • DOI: 10.1007/s00018-020-03740-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Systematic Analysis of Targets of Pumilio-mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis (2020)
  • Author(s): Toshimichi Yamada, Naoto Imamachi, Katsutoshi Imamura, Kenzui Taniue, Takeshi Kawamura, Yutaka Suzuki, Masami Nagahama, Nobuyoshi Akimitsu
  • Journal Title: Cell Reports Volume: - Issue: 5 Pages: 107542-107542
  • DOI: 10.1016/j.celrep.2020.107542
  • Peer Reviewed / Open Access / Int'l Joint Research