Development of chip device to detect methylations on microRNAs

• Project/Area Number: 15K15474
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: Nishida Naohiro 大阪大学, 医学系研究科, 助教 (50588118)
• Co-Investigator(Kenkyū-buntansha): 今野 雅允 大阪大学, 医学系研究科, 寄附講座助教 (80618207) ; 川本 弘一 大阪大学, 医学系研究科, 特任助教(常勤) (30432470) ; 小関 準 大阪大学, 医学系研究科, 特任助教(常勤) (20616669) ; 石井 秀始 大阪大学, 医学系研究科, 特任教授(常勤) (10280736)
• Co-Investigator(Renkei-kenkyūsha): Mori Masaki 大阪大学, 大学院医学系研究科, 教授 (70190999) ; Obika Satoshi 大阪大学, 大学院薬学系研究科, 教授 (80243252)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 核酸 / 癌 / 遺伝子 / 臨床

Outline of Final Research Achievements

Chemical modifications of microRNA molecules potentially alter their biological functions. This study is aimed for a development of devices to comprehensively detect methylations of small nucleotide molecules including microRNAs. Efficient purifications of target microRNAs and highly accurate detection using mass spectrometry are key processes of this system. We have developed target enrichment method using affinity chromatography to precisely quantify chemical modifications on microRNAs from a very few amount of RNA samples. Furthermore, the optimizations of mass spectrometry settings including improvement of ionization efficiency and adjustment of measurement ranges enabled detection of a very small amount of chemical modifications (less than 5%) on microRNA oligonucleotides. To detect variety kinds of chemical modifications on many microRNA species, we have designed chip devices, on which oligonucleotides with complement DNA sequence of target microRNAs are densely printed.

Research Products

• [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] 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] 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] 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] The combination of the expression of hexokinase 2 and pyruvate kinase M2 is a prognostic marker in patients with pancreatic cancer. (2015)
  • Author(s): Ogawa, H., Nagano, H., Konno, M., Eguchi, H., Koseki, J., Kawamoto, K., Nishida, N., Colvin, H., Tomokuni, A., Tomimaru, Y., Hama, N., Wada, H., Marubashi, S., Kobayashi, S., Mori, M., Doki, Y., Ishii, H.
  • Journal Title: Mol Clin Oncol. Volume: 3 Pages: 563-571
  • Peer Reviewed
• [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
• [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
• [Presentation] Epigenetic modifications on non-coding RNAs in cancer (2017)
  • Author(s): Nishida, N., Konno, M., Koseki, J., Kawamoto, K., Asai, A., Mizushima, T., Eguchi, H., Takiguchi, S., Satoh, T., Doki, Y., Mori, 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] 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、三森 功士、落谷 孝広、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