New development of epigenome drug discovery to realize oncogene selectivity

• Project/Area Number: 16K15592
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: SATOH Taroh 大阪大学, 医学系研究科, 寄附講座教授 (40368303)
• Co-Investigator(Kenkyū-buntansha): 西田 尚弘 大阪大学, 医学系研究科, 助教 (50588118) ; 今野 雅允 大阪大学, 医学系研究科, 寄附講座講師 (80618207) ; 川本 弘一 大阪大学, 医学部附属病院, その他 (30432470) ; 小関 準 大阪大学, 医学系研究科, 特任助教(常勤) (20616669) ; 工藤 敏啓 大阪大学, 医学系研究科, 寄附講座助教 (20593859) ; 坂井 大介 大阪大学, 医学系研究科, 寄附講座助教 (10621071)
• Co-Investigator(Renkei-kenkyūsha): ISHII Hideshi 大阪大学, 大学院医学系研究科, 特任教授 (10280736) ; MORI Masaki 大阪大学, 大学院医学系研究科, 教授 (70190999)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌 / 酵素

Outline of Final Research Achievements

To target an oncogene in clinical setting, it is important to develop effective drug discovery based on the accurate information in epigenome. In the present study, the histone demethylating enzyme controlled by oncogene c - MYC was identified as a target candidate by using the comprehensive transcriptome analysis method. As a result, it was shown that histone methylation modification system was important and that NO66 played an important role in gastrointestinal cancer as its target. Furthermore we showed that it was possible to overcome refractory cancer by drug discovery targeting MYC - NO 66, for which we constructed the foundation.

Research Products

• [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] 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] 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] 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] 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] 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
• [Journal Article] Clinical significance of histone demethylase NO66 in invasive colorectal cancer. (2017)
  • Author(s): Nishizawa, Y., Nishida, N., Konno, M., Kawamoto, K., Asai, A., Koseki, J., Takahashi, H., Haraguchi, N., Nishimura, J., Hata, T., Matsuda, C., Mizushima, T., Satoh, T., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Ann. Surg. Oncol. Volume: 24 Issue: 3 Pages: 841-849
  • DOI: 10.1245/s10434-016-5395-9
  • Peer Reviewed / Open Access
• [Journal Article] Oncometabolite D-2-hydroxyglurate directly induces epithelial-mesenchymal transition and is associated with distant metastasis in colorectal cancer. (2016)
  • Author(s): Colvin, S. H., Nishida, N., Konno, M., Haraguchi, N., Takahashi, H., Nishimura, J., Hata, T., Kawamoto, K. Asai, A., Tsunekuni, K., Koseki, J., Mizushima, T., Satoh, T., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Sci. Rep Volume: 6 Issue: 1 Pages: 36289-36289
  • DOI: 10.1038/srep36289
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of capecitabine and S-1 on anticoagulant activity of warfarin in patients with gastrointestinal cancer. (2016)
  • Author(s): Hata, T., Kudo, T., Sakai, D., Takahashi, H., Haraguchi, N., Nishimura, J., Hata, T., Mizushima, T., Yamamoto, H., Doki, Y., Mori, M., Satoh, T.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 78 Issue: 2 Pages: 389-396
  • DOI: 10.1007/s00280-016-3080-0
  • Peer Reviewed / Open Access
• [Presentation] ヒストンメチル化酵素 KDM5B の消化器がん進展への関わり (2017)
  • Author(s): 西田 尚弘、太田 勝也、加納 義浩、小関 準、今野 雅允、浅井 歩、川本 弘一、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] 転移性癌幹細胞に特異的な代謝機構の究明 (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26回日本がん転移学会学術集会・総会
• [Presentation] 消化器癌の悪性度に関わるメカノバイオロジー (2017)
  • Author(s): 今野 雅允、松下 克則、柳澤 公紀、佐藤 太郎、出口 真次、土 岐 祐一郎、森 正樹、石井 秀始
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 新規トランスオミックス法を用いたがん幹細胞における化学療法耐性 の解析 (2017)
  • 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76回日本癌学会学術総会