Targeting and clinical application of m6A epitranscriptome for refractory gastrointestinal cancer

• Project/Area Number: 18K16355
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Asai Ayumu 大阪大学, 産業科学研究所, 特任助教(常勤) (40783262)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: エピトランスクリプトーム / 先端計測 / バイオマーカー

Outline of Final Research Achievements

In order to apply measurements of methylated adenosine (m6A) in miRNA to cancer diagnosis, we have established a measurement method for m6A with a measurement technology we developed.
In addition, we identified methylated miRNAs in gastrointestinal cancer cells by measuring methylated miRNAs in cultured cells.
Furthermore, we compared with existing diagnostic markers in patients with early-stage cancer. As a result, the existing diagnostic markers could not discriminate between early cancer and healthy control, but the measurement of methylated miRNA succeeded in discriminating them. No diagnostic method that can detect early cancer with high accuracy have been developed, so our research results would greatly contribute to the early detection and treatment of cancer in the future.

Academic Significance and Societal Importance of the Research Achievements

これまでに、がん細胞においてm6Aの重要性が報告されていたが、実際のがん患者でm6Aを計測した実例はなく、m6Aの計測方法も確立されていなかった。
我々はヒト検体におけるm6Aの計測方法を確立したことから、今後がん以外にもm6Aの研究が発展する可能性を示したことから、学術的にも大変意義深い。
また、早期がんを高精度に判別可能な診断方法は存在しなかったため、我々の成果は今後のがんの早期発見・早期治療に貢献し、臨床的にも経済的にも波及効果をもたらす。

Research Products

• [Journal Article] Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA (2020)
  • Author(s): Koseki Jun、Konno Masamitsu、Asai Ayumu、Horie Naohiro、Tsunekuni Kenta、Kawamoto Koichi、Obika Satoshi、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 1138-1138
  • DOI: 10.1038/s41598-020-57899-7
  • Peer Reviewed / Open Access
• [Journal Article] One-carbon metabolism for cancer diagnostic and therapeutic approaches (2020)
  • Author(s): Asai Ayumu、Konno Masamitsu、Koseki Jun、Taniguchi Masateru、Vecchione Andrea、Ishii Hideshi
  • Journal Title: Cancer Letters Volume: 470 Pages: 141-148
  • DOI: 10.1016/j.canlet.2019.11.023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure (2019)
  • Author(s): Tsunekuni Kenta、Konno Masamitsu、Haraguchi Naotsugu、Koseki Jun、Asai Ayumu、Matsuoka Kazuaki、Kobunai Takashi、Takechi Teiji、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 14861-14861
  • DOI: 10.1038/s41598-019-50968-6
  • Peer Reviewed / Open Access
• [Journal Article] Distinct methylation levels of mature microRNAs in gastrointestinal cancers (2019)
  • Author(s): Konno Masamitsu、Koseki Jun、Asai Ayumu、Yamagata Akira、Shimamura Teppei、Motooka Daisuke、Okuzaki Daisuke、Kawamoto Koichi、Mizushima Tsunekazu、Eguchi Hidetoshi、Takiguchi Shuji、Satoh Taroh、Mimori Koshi、Ochiya Takahiro、Doki Yuichiro、Ofusa Ken、Mori Masaki、Ishii Hideshi
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 3888-3888
  • DOI: 10.1038/s41467-019-11826-1
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance (2019)
  • Author(s): Takaoka Yuji、Konno Masamitsu、Koseki Jun、Colvin Hugh、Asai Ayumu、Tamari Keisuke、Satoh Taroh、Mori Masaki、Doki Yuichiro、Ogawa Kazuhiko、Ishii Hideshi
  • Journal Title: Cancer Science Volume: 110 Issue: 4 Pages: 1331-1339
  • DOI: 10.1111/cas.13980
  • Peer Reviewed / Open Access
• [Journal Article] Direct Analysis of Incorporation of an Anticancer Drug into DNA at Single-Molecule Resolution (2019)
  • Author(s): Ohshiro Takahito、Komoto Yuuki、Konno Masamitsu、Koseki Jun、Asai Ayumu、Ishii Hideshi、Taniguchi Masateru
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 3886-3886
  • DOI: 10.1038/s41598-019-40504-x
  • Peer Reviewed / Open Access
• [Journal Article] Association of iron metabolic enzyme hepcidin expression levels with the prognosis of patients with pancreatic cancer (2018)
  • Author(s): Toshiyama Reishi、Konno Masamitsu、Eguchi Hidetoshi、Asai Ayumu、Noda Takehiro、Koseki Jun、Asukai Kei、Ohashi Tomofumi、Matsushita Katsunori、Iwagami Yoshifumi、Yamada Daisaku、Asaoka Tadafumi、Wada Hiroshi、Kawamoto Koichi、Gotoh Kunihito、Kudo Toshihiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncology Letters Volume: 15 Pages: 8125-8133
  • DOI: 10.3892/ol.2018.8357
  • Peer Reviewed / Open Access
• [Journal Article] Poly(ethylene glycol)ーpoly(lysine) block copolymerーubenimex conjugate targets aminopeptidase N and exerts an antitumor effect in hepatocellular carcinoma stem cells (2018)
  • Author(s): Toshiyama, R., Konno, M., Eguchi, H., Takemoto, H., Noda, T., Asai, A., Koseki, J., Haraguchi, N., Ueda, Y. Matsushita, K., Asukai, K., Ohashi, T., Iwagami, Y., Yamada, D., Sakai, D., Asaoka, T., Kudo, T., Kawamoto, K., Gotoh, K., Kobayashi, S., Satoh, T., Doki, Y., Nishiyama, N., Mori, M., Ishii, H.
  • Journal Title: Oncogene Volume: 38 Issue: 2 Pages: 244-260
  • DOI: 10.1038/s41388-018-0406-x
  • Peer Reviewed / Open Access
• [Journal Article] A Convolutional Neural Network Uses Microscopic Images to Differentiate between Mouse and Human Cell Lines and Their Radioresistant Clones (2018)
  • Author(s): Toratani Masayasu、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kawamoto Koichi、Tamari Keisuke、Li Zhihao、Sakai Daisuke、Kudo Toshihiro、Satoh Taroh、Sato Katsutoshi、Motooka Daisuke、Okuzaki Daisuke、Doki Yuichiro、Mori Masaki、Ogawa Kazuhiko、Ishii Hideshi
  • Journal Title: Cancer Research Volume: 78 Issue: 23 Pages: 6703-6707
  • DOI: 10.1158/0008-5472.can-18-0653
  • Peer Reviewed / Open Access
• [Journal Article] Drug discovery of anticancer drugs targeting methylenetetrahydrofolate dehydrogenase 2 (2018)
  • Author(s): Asai Ayumu、Koseki Jun、Konno Masamitsu、Nishimura Tatsunori、Gotoh Noriko、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Heliyon Volume: 4 Issue: 12 Pages: e01021-e01021
  • DOI: 10.1016/j.heliyon.2018.e01021
  • Peer Reviewed / Open Access
• [Journal Article] Polyamine flux suppresses histone lysine demethylases and enhances ID1 expression in cancer stem cells (2018)
  • Author(s): Tamari K, KonnoM , Asai A, Koseki J, Hayashi K, Kawamoto K, Murai N, Matsufuji S, Isohashi F, Satoh T, Gotoh N, Tanaka S, Doki Y, Mori M, Ogawa K, Ishii H.
  • Journal Title: Cell Death Discovery Volume: 4 Issue: 104 Pages: 104-104
  • DOI: 10.1038/s41420-018-0117-7
  • Peer Reviewed / Open Access
• [Presentation] 膵がんの悪性化に関わるエピトランスクリプトーム制御 (2018)
  • Author(s): 浅井歩、今野雅允、小関準、佐藤太郎、後藤典子、土岐祐一郎、 森正樹、石井秀始
  • Organizer: 第６回がんと代謝研究会