Elucidation of microRNA methylation mechanism for high precision cancer diagnosis

• Project/Area Number: 15H05664
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: NISHIDA Naohiro 大阪大学, 医学系研究科, 助教 (50588118)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000); Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2015: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 癌 / 臨床 / 遺伝子 / 核酸

Outline of Final Research Achievements

By recent studies of the RNA methylation mechanism, it has been known that the RNA functions as an important regulator of gene expression by dynamically converting its methylation state as the DNA and histone do. In the present study, we then clarified the clinical significance of methylated miRNAs by the comprehensive profiling in cancer and improved accuracy of miRNAs as cancer biomarkers by studying the methylation. As a result, the mechanism of microRNA methylation was clarified and we constructed further the foundation for accurate diagnosis in the precision medicine.

Research Products

• [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] 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] The importance of mitochondrial folate enzymes in human colorectal cancer. (2017)
  • Author(s): Miyo, M., Konno, M., Colvin, S. H., Nishida, N., Koseki, J., Kawamoto, K., Tsunekuni, K., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Oncol. Rep. Volume: 37 Issue: 1 Pages: 417-425
  • DOI: 10.3892/or.2016.5264
  • 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] Metabolic adaptation to nutritional stress in human colorectal cancer. (2016)
  • Author(s): Miyo, M., Konno, M., Nishida, N. Sueda, T., Noguchi, K., Matsui, H., Colvin, H., Kawamoto, K., Koseki, J., Haraguchi, N., Nishimura, J., Hata, T., Gotoh, N., Mastuda, F., Saatoh, T., Mizushima, T., Shimizu, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 38415-38415
  • DOI: 10.1038/srep38415
  • 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] MicroRNA miR-374, a potential radiosensitizer for carbon ion beam radiotherapy. (2016)
  • Author(s): Baek, SJ., Sato, K., Nishida, N., Koseki, J., Azuma, R., Kawamoto, K., Konno, M., Hayashi, K., Satoh, T., Doki, Y., Mori, M., Ishii, H., Ogawa, K.
  • Journal Title: Oncol. Rep. Volume: 36 Issue: 5 Pages: 2946-2950
  • DOI: 10.3892/or.2016.5122
  • Peer Reviewed / Open Access
• [Journal Article] Pancreaticoduodenal artery aneurysm associated with coeliac artery occlusion from an aortic intramural hematoma. (2016)
  • Author(s): Sakatani, A., Doi, Y., Kitayama, T., Matsuda, T., Sasai, Y., Nishida, N., Sakamoto, M., Uenoyama, N., Kinoshita, K.
  • Journal Title: World. J. Gastroenterol. Volume: 22 Issue: 16 Pages: 4259-4263
  • DOI: 10.3748/wjg.v22.i16.4259
  • Peer Reviewed / Open Access
• [Journal Article] A crucial epithelial to mesenchymal transition regulator, Sox4/Ezh2 axis is closely related to the clinical outcome in pancreatic cancer patients. (2016)
  • Author(s): Hasegawa, S., Nagano, H., Konno, M., Eguchi, H., Tomokuni, A., Tomimaru, Y., Asaoka, T., Wada, H., Hama, N., Kawamoto, K., Marubashi, S., Nishida, N., Koseki, J., Mori, M., Doki, Y., Ishii, H.
  • Journal Title: Int J Oncol. Volume: 48 Issue: 1 Pages: 145-152
  • DOI: 10.3892/ijo.2015.3258
  • Peer Reviewed
• [Journal Article] A Trans-omics Mathematical Analysis Reveals Novel Functions of the Ornithine Metabolic Pathway in Cancer Stem Cells. (2016)
  • Author(s): Koseki, J., Matsui, H., Konno, M., Nishida, N., Kawamoto, K., Kano, Y., Mori, M., Doki, Y., Ishii, H.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 20726-20726
  • DOI: 10.1038/srep20726
  • Peer Reviewed / Open Access
• [Journal Article] Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG-inactivating β-oxygenation pathway in colorectal cancer (2015)
  • Author(s): Koseki, J., Colvin, H., Fukusumi, T., Nishida, N., Konno, M., Kawamoto, K., Tsunekuni, K., Matsui, H., Doki, Y., Mori, M. and Ishii, H.
  • Journal Title: International Journal of Oncology Volume: 46 Issue: 3 Pages: 1181-1191
  • DOI: 10.3892/ijo.2015.2833
  • Peer Reviewed
• [Journal Article] Pyruvate kinase M2, but not M1, allele maintains immature metabolic states of murine embryonic stem cells (2015)
  • Author(s): Konno, M., Ishii, H., Koseki, J., Tanuma, N., Nishida, N., Kawamoto, K., Nishimura, T., Nakata, A., Matsui, H., Noguchi, K., Ozaki, M., Noguchi, Y., Shima, H., Gotoh N., Nagano, H., Doki, Y. and Mori, M.
  • Journal Title: Regenerative Therapy Volume: 1 Pages: 63-71
  • DOI: 10.1016/j.reth.2015.01.001
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNAs induce epigenetic reprogramming and suppress malignant phenotypes of human colon cancer cells. (2015)
  • Author(s): Ogawa, H., Wu, X., Kawamoto, K., Nishida, N., Konno, M., Koseki, J., Matsui, H., Noguchi, K., Gotoh, N., Yamamoto, T., Miyata, K., Nishiyama, N., Nagano, H., Yamamoto, H., Obika, S., Kataoka, K., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: PLoS One. Volume: 10 Issue: 5 Pages: 1-23
  • DOI: 10.1371/journal.pone.0127119
  • Peer Reviewed / Open Access
• [Journal Article] Cancer stem cells: The potential of carbon ion beam radiation and new radiosensitizers (Review). (2015)
  • Author(s): Baek, SJ., Ishii, H., Tamari, K., Hayashi, K., Nishida, N., Konno, M., Kawamoto, K., Koseki, J., Fukusumi, T., Hasegawa, S., Ogawa, H., Hamabe, A., Miyo, M., Noguchi, K., Seo, Y., Doki, Y., Mori, M., Ogawa, K.
  • Journal Title: Oncol Rep. Volume: 34 Issue: 5 Pages: 2233-2237
  • DOI: 10.3892/or.2015.4236
  • Peer Reviewed / Open Access
• [Journal Article] Susceptibility of pancreatic cancer stem cells to reprogramming. (2015)
  • Author(s): Noguchi, K., Eguchi, H., Konno, M., Kawamoto, K., Nishida, N., Koseki, J., Wada, H., Marubashi, S., Nagano, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Cancer Sci. Volume: 106 Issue: 9 Pages: 1182-1187
  • DOI: 10.1111/cas.12734
  • Peer Reviewed / Open Access
• [Journal Article] Embryonic microRNA-369 controls metabolic splicing factors and urges cellular reprograming. (2015)
  • Author(s): Masamitsu Konno, Jun Koseki, Koichi Kawamoto, Naohiro Nishida, Hidetoshi Matsui, Dyah Laksmi Dewi, Miyuki Ozaki, Yuko Noguchi, Koshi Mimori, Noriko Gotoh, Nobuhiro Tanuma, Hiroshi Shima, Yuichiro Doki, Masaki Mori , Hideshi Ishii
  • Journal Title: PLOS ONE Volume: 10(7) Issue: 7 Pages: 1-16
  • DOI: 10.1371/journal.pone.0132789
  • Peer Reviewed / Open Access
• [Presentation] Epigenetic modifications on non-coding RNAs in cancer (2017)
  • Author(s): Nishida, N., Konno, M., Koseki, Jun., Kawamoto, Koichi., Asai, Ayumu., Mizushima, T., Eguchi, H., Takiguchi, S., Satoh, T., Doki, Y., Mori1, M., Ishii, H.,
  • Organizer: 2017 Cellular and Molecular Bioengineering Annual Conference
  • Place of Presentation: Hapuna Beach Prince Hotel (アメリカ）
  • Year and Date: 2017-01-03
  • Int'l Joint Research
• [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] 大腸がんにおけるヒストン脱メチル化酵素N066の臨床的意義の解明 (2017)
  • Author(s): 西沢佑次郎、西田尚弘、今野雅允、川本弘一、小関準、浅井歩、西村潤一、畑康司、松田宙、佐藤太郎、水島恒和、山本浩文、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] 長鎖ノンコーディングRNAの大腸癌におけるエピゲノム制御 (2017)
  • Author(s): 西田 尚弘、Jana Ferdin、今野 雅允、小関 準、川本 弘一、 浅井 歩、George Calin、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] 大腸癌進展におけるヒストン脱メチル化酵素NO66の重要性 (2017)
  • Author(s): 西沢 佑次郎、西田 尚弘、今野 雅允、川本 弘一、小関 準、浅井歩、西村 潤一、畑 泰司、松田 宙、水島 恒和、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] 臨床情報が裏付けるノンコーディングRNAエピゲノム修飾の意義 (2016)
  • Author(s): 西田尚弘、大房健、山縣彰、小関準、今野雅允、川本弘一、浅井歩、水島恒和、江口英利、瀧口修司、佐藤太郎、落谷孝広、三森功士、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川）
  • Year and Date: 2016-11-30
• [Presentation] 消化器癌におけるヒストン脱メチル化酵素の標的化 (2016)
  • Author(s): 西田 尚弘、小関 準、今野 雅允、川本 弘一、太田 勝也、土岐祐一郎、森 正樹、石井 秀始
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川）
  • Year and Date: 2016-10-06
• [Presentation] ノンコーディングRNAの消化器癌進展への関わり (2015)
  • Author(s): 西田尚弘、Ferdin Jana、今野雅允、小関準、川本弘一、Calin George、三森功士、石井秀始、森正樹
  • Organizer: 第26回日本消化器癌発生学会総会
  • Place of Presentation: 米子全日空ホテル（鳥取）
  • Year and Date: 2015-11-19
• [Presentation] ヒストン脱メチル化酵素KDM5B の大腸癌進展機構への関わり (2015)
  • Author(s): 西田尚弘、太田勝也、加納義浩、小関準、今野雅允、川本弘一、溝端栄一、井上豪、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知）
  • Year and Date: 2015-10-08
• [Presentation] Cell cycle regulation of KDM5B and its involvement in cancer progression. (2015)
  • Author(s): Nishida N, Koseki J, Konno M, Kawamoto K, Ohta K, Kano Y, Doki Y, Mori M, Ishii H.
  • Organizer: Cell Symposia Multifaceted Mitochondria
  • Place of Presentation: Hyatt Regency McCormick Place(アメリカ）
  • Year and Date: 2015-07-19
  • Int'l Joint Research
• [Presentation] KDM5B plays a central role in esophageal cancer progression. (2015)
  • Author(s): Nishida N, Kano Y, Koseki J, Konno M, Kawamoto K, Doki Y, Mori M, Ishii H.
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: PENNSYLVANIA CONVENTION CENTER（アメリカ）
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] がんを検出、又はがんの進行期を判定する方法 (2016)
  • Inventor(s): 石井秀始、西田尚弘...大房健 他8
  • Industrial Property Rights Holder: 石井秀始、西田尚弘...大房健 他8
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-162203
  • Filing Date: 2016-08-22