Grasp of tissue homeostasis by microRNA modomics and clinical application

• Project/Area Number: 17K19698
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Osaka University
• Principal Investigator: Ishii Hideshi 大阪大学, 医学系研究科, 特任教授(常勤) (10280736)
• Co-Investigator(Kenkyū-buntansha): 今野 雅允 大阪大学, 医学系研究科, 寄附講座講師 (80618207) ; 小関 準 大阪大学, 医学系研究科, 特任助教(常勤) (20616669)
• Research Collaborator: MORI masaki ; DOKI yuichiro ; EGUCHI hidetoshi ; TANIGUCHI masateru ; KAWAMOTO koichi
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 癌 / ゲノム / 細胞・組織 / トンネル現象 / 核酸

Outline of Final Research Achievements

There is no established technique for deciphering chemical modification at the single base level of microRNA. Two closely complementary techniques were applied to precisely profile the modality of total microRNAs. Accurate measurement of intramolecular modification by mass spectrometry, and accumulation of data of short sequence by tunneling current sequence (TS) method was performed. We studied a new viewpoint by advancing the modulomic analysis of single cell level microRNA by the above measurement technology to understand the mechanisms of tissue homeostasis. We studied the development and carcinogenesis of the pancreas using genetically modified mice of microRNA methylation enzymes, and proceeded to understand the role of RNA modus in carcinogenesis from somatic stem cells in human diseases.

Academic Significance and Societal Importance of the Research Achievements

マイクロRNAの科学修飾を解読してデータベース化する研究は、先駆的であり、まだ十分に行われていないため、本研究計画においてその全容を明らかにすることは大きな意義がある。特に、他のオミックスデータと融合させた形で、マイクロRNAのモドミクスにより組織の恒常性を把握して、難治癌などの早期発見と早期治療に貢献できる臨床応用には社会的意義が高いと考えられる。

Research Products

• [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] Cell?free culture conditioned medium elicits pancreatic β cell lineage?specific epigenetic reprogramming in mice (2018)
  • Author(s): Kawamoto Koichi、Ohashi Tomofumi、Konno Masamitsu、Nishida Naohiro、Koseki Jun、Matsui Hidetoshi、Sakai Daisuke、Kudo Toshihiro、Eguchi Hidetoshi、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncology Letters Volume: 16 Pages: 3255-3259
  • DOI: 10.3892/ol.2018.9008
  • Peer Reviewed / Open Access
• [Journal Article] Carbon ion beam radioresistant rodent cells are sensitized to trifluorothymidine exposure (2018)
  • Author(s): Baek Sung Jae、Sato Katsutoshi、Nishida Naohiro、Koseki Jun、Hayashi Kazuhiko、Kawamoto Koichi、Konno Masamitsu、Doki Yuichiro、Mori Masaki、Ogawa Kazuhiko、Ishii Hideshi
  • Journal Title: Oncology Letters Volume: 16 Pages: 3389-3393
  • DOI: 10.3892/ol.2018.9004
  • 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] 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
• [Journal Article] Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells (2018)
  • Author(s): Tominaga, K., Minato, H., Murayama, T., Sasahara, A., Nishimura, T., Kiyokawa, E., Kanauchi, H., Shimizu, S., Sato, A., Nishioka, K., Tsuji, E., Yano, M., Ogawa, T., Ishii, H., Mori, M., Akashi, K., Okamoto, K., Tanabe, M., Tada, K., Tojo, A., Gotoh, N.
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 116 Issue: 2 Pages: 625
  • DOI: 10.1073/pnas.1806851116
  • URL: https://pure.teikyo.jp/en/publications/27ae2888-ba87-4c3b-8682-38ab484315f4
  • Peer Reviewed / Open Access
• [Journal Article] Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis (2018)
  • Author(s): Koseki Jun、Konno Masamitsu、Asai Ayumu、Colvin Hugh、Kawamoto Koichi、Nishida Naohiro、Sakai Daisuke、Kudo Toshihiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 303-303
  • DOI: 10.1038/s41598-017-18456-x
  • Peer Reviewed / Open Access
• [Journal Article] Computational trans-omics approach characterised methylomic and transcriptomic involvements and identified novel therapeutic targets for chemoresistance in gastrointestinal cancer stem cells (2018)
  • Author(s): Konno Masamitsu、Matsui Hidetoshi、Koseki Jun、Asai Ayumu、Kano Yoshihiro、Kawamoto Koichi、Nishida Naohiro、Sakai Daisuke、Kudo Toshihiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 899-899
  • DOI: 10.1038/s41598-018-19284-3
  • Peer Reviewed / Open Access
• [Journal Article] The one-carbon metabolism pathway highlights therapeutic targets for gastrointestinal cancer (Review) (2017)
  • Author(s): Konno Masamitsu、Asai Ayumu、Kawamoto Koichi、Nishida Naohiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Int. J. Oncol. Volume: 50 Issue: 4 Pages: 1057-1063
  • DOI: 10.3892/ijo.2017.3885
  • Peer Reviewed / Open Access
• [Journal Article] Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism (2017)
  • Author(s): Yamada Naoki、Honda Yuto、Takemoto Hiroyasu、Nomoto Takahiro、Matsui Makoto、Tomoda Keishiro、Konno Masamitsu、Ishii Hideshi、Mori Masaki、Nishiyama Nobuhiro
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 6077-6077
  • DOI: 10.1038/s41598-017-06438-y
  • Peer Reviewed / Open Access
• [Journal Article] Low expression of the GOPC is a poor prognostic marker in colorectal cancer (2017)
  • Author(s): Ohara Nobuyoshi、Haraguchi Naotsugu、Koseki Jun、Nishizawa Yujiro、Kawai Kenji、Takahashi Hidekazu、Nishimura Junichi、Hata Taishi、Mizushima Tsunekazu、Yamamoto Hirofumi、Ishii Hideshi、Doki Yuichiro、Mori Masaki
  • Journal Title: Oncol. Lett. Volume: 14 Issue: 4 Pages: 4483-4490
  • DOI: 10.3892/ol.2017.6817
  • Peer Reviewed / Open Access
• [Journal Article] Micro-RNA-130a-3p Regulates Gemcitabine?Resistance via PPARG in Cholangiocarcinoma (2017)
  • Author(s): Asukai Kei、Kawamoto Koichi、Eguchi Hidetoshi、Konno Masamitsu、Asai Ayumu、Iwagami Yoshifumi、Yamada Daisaku、Asaoka Tadafumi、Noda Takehiro、Wada Hiroshi、Gotoh Kunihito、Nishida Naohiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Ann. Surg. Oncol. Volume: 24 Issue: 8 Pages: 2344-2352
  • DOI: 10.1245/s10434-017-5871-x
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA profiles involved in trifluridine resistance (2017)
  • Author(s): Tsunekuni Kenta、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kobunai Takashi、Takechi Teiji、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncotarget. Volume: 8 Issue: 32 Pages: 53017-53027
  • DOI: 10.18632/oncotarget.18078
  • Peer Reviewed / Open Access
• [Journal Article] The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells (2017)
  • Author(s): Taketo Kosuke、Konno Masamitsu、Asai Ayumu、Koseki Jun、Toratani Masayasu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi、Ogawa Kazuhiko
  • Journal Title: Int. J. Oncol. Volume: 52 Pages: 621-629
  • DOI: 10.3892/ijo.2017.4219
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia stimulates the cytoplasmic localization of oncogenic long noncoding RNA LINC00152 in colorectal cancer (2017)
  • Author(s): Nishizawa Yujiro、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kawamoto Koichi、Miyoshi Norikatsu、Takahashi Hidekazu、Nishida Naohiro、Haraguchi Naotsugu、Sakai Daisuke、Kudo Toshihiro、Hata Taishi、Matsuda Chu、Mizushima Tsunekazu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Int. J. Oncol. Volume: 52 Pages: 453-460
  • DOI: 10.3892/ijo.2017.4218
  • Peer Reviewed / Open Access
• [Journal Article] Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer (2017)
  • Author(s): Nishizawa Yujiro、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kawamoto Koichi、Miyoshi Norikatsu、Takahashi Hidekazu、Nishida Naohiro、Haraguchi Naotsugu、Sakai Daisuke、Kudo Toshihiro、Hata Taishi、Matsuda Chu、Mizushima Tsunekazu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncotarget. Volume: 9 Issue: 7 Pages: 7476-7486
  • DOI: 10.18632/oncotarget.23554
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma (2017)
  • Author(s): Ohashi Tomofumi、Eguchi Hidetoshi、Kawamoto Koichi、Konno Masamitsu、Asai Ayumu、Colvin Hugh、Ueda Yuji、Takaoka Hirofumi、Iwagami Yoshifumi、Yamada Daisaku、Asaoka Tadafumi、Noda Takehiro、Wada Hiroshi、Gotoh Kunihito、Kobayashi Shogo、Koseki Jun、Satoh Taroh、Ogawa Kazuhiko、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncol. Rep. Volume: 39 Pages: 1276-1282
  • DOI: 10.3892/or.2017.6172
  • Peer Reviewed / Open Access
• [Presentation] Generation of invasion model of colorectal cancer with three-dimensional culture method. (2019)
  • Author(s): Yanagisawa, K., Konno, M., Asai, A., Koseki, J., Mizushima, T., Satoh, T., Matsuzaki, M., Doki, Y., Ishii, H.
  • Organizer: Single Cells: Technology to Biology Cell Symposia
  • Int'l Joint Research
• [Presentation] Trifluridine efficacy in cancer stem cell (2018)
  • Author(s): 常國健太、今野雅允、小関準、浅井歩、土岐祐一郎、森正樹、石井秀始
  • Organizer: AACR Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] 新規トランスオミックス法を用いたがん幹細胞のDNAメチル化量及び転写量変化の相関解析 (2018)
  • Author(s): 小関準、今野雅允、浅井歩、佐藤太郎、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第６回がんと代謝研究会
• [Presentation] 糖代謝酵素のスプライシング変化による認知症発症機構の解明 (2018)
  • Author(s): 今野雅允、浅井歩、田沼延公、島礼、小関準、佐藤太郎、 土岐祐一郎、森正樹、石井秀始
  • Organizer: 第６回がんと代謝研究会
• [Presentation] CD44/CD133-Positive Colorectal Cancer Stem Cells Are Sensitive to Trifluridine (2018)
  • Author(s): 常國健太、今野雅允、小関準、浅井歩、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第６回がんと代謝研究会
• [Presentation] 消化器がん幹細胞のエピゲノム異常の標的化と制御 (2018)
  • Author(s): 小関準、浅井歩、今野雅允、佐藤太郎、土岐祐一郎、辻川和丈、森正樹、石井秀始
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] がんエピトランスクリプトームの解明と応用 (2018)
  • Author(s): 今野雅允、佐藤太郎、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] 臨床からみた癌幹細胞と免疫微小環 (2018)
  • Author(s): 田中真二 (座長：石井秀始）
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] がんエピトランスクリプトーム研究の新展開 (2018)
  • Author(s): 石井秀始
  • Organizer: 第29回日本消化器癌発生学会総会
• [Presentation] 消化器癌の浸潤に関わる分子メカニズムの解明と治療への応用 (2018)
  • Author(s): 泥谷直樹 (座長：石井秀始）
  • Organizer: 第9回 癌・炎症と抗酸化研究会
• [Presentation] 消化器がん幹細胞の代謝制御 (2017)
  • Author(s): 今野雅允、三代雅明、浜部敦史、佐藤太郎、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第5回がんと代謝研究会 in 札幌
• [Presentation] 癌幹細胞のビックデータサイエンス (2017)
  • Author(s): 石井秀始
  • Organizer: 第26回日本がん転移学会学術集会・総会
• [Presentation] トランス-オミックス法を用いたがん幹細胞におけるポリアミン代謝経路の意義の解析 (2017)
  • Author(s): 小関準、今野雅允、松井秀俊、加納義弘、佐藤太郎、森正樹、土岐祐一郎、石井秀始
  • Organizer: 第26回日本がん転移学会学術集会・総会
• [Presentation] 癌幹細胞とOne Carbon代謝創薬 (2017)
  • Author(s): 石井秀始
  • Organizer: 第26回日本がん転移学会学術集会・総会
• [Presentation] がん幹細胞の代謝、エピゲノム、マーカー、そして創薬 (2017)
  • Author(s): 石井秀始
  • Organizer: 第55回日本癌治療学会学術集会
• [Patent(Industrial Property Rights)] RNAモドミクスによるコンパニオン診断、創薬 (2018)
  • Inventor(s): 石井秀始、今野雅允、森正樹
  • Industrial Property Rights Holder: 石井秀始、今野雅允、森正樹
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-030099
  • Filing Date: 2018