Investigation of inhibitor molecules focusing on cytoplasmic polyadenylation complex in epithelial malignant tumor

• Project/Area Number: 17H03923
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: NAGAOKA KENTARO 東京農工大学, (連合)農学研究科(研究院), 教授 (60376564)
• Co-Investigator(Kenkyū-buntansha): 藤田 知之 順天堂大学, 医学部, 先任准教授 (00419392) ; 金蔵 孝介 東京医科大学, 医学部, 講師 (10508568) ; 伊藤 昌彦 浜松医科大学, 医学部, 助教 (50385423)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 乳癌 / 転写後調節 / 低分子化合物 / 乳がん / ポリアデニル化複合体 / CPEB1 / 低分子化合物スクリーニング / 上皮悪性腫瘍 / ポリA鎖

Outline of Final Research Achievements

Cytoplasmic polyadenylation is a phenomenon that stretches and contracts the poly-A tail of mRNA in the cytoplasm, and CPEB1 is known to be the master gene. Analysis of human and cat clinical samples confirmed that CPEB1 gene expression was down-regulated in breast cancer tissues compared to normal tissues, demonstrating the potential of CPEB1 as a breast cancer suppressor gene. We also performed gene profiling according to the length of the poly-A tail in each subtype of breast cancer. Furthermore, the in vitro assay system identified 29 small molecule compounds that increased CPEB1 expression, which are potential seeds that could lead to novel breast cancer suppression and treatment drugs.

Academic Significance and Societal Importance of the Research Achievements

癌は日本人の「国民病」と称され、現代の高齢化社会と相まって癌に罹患する可能性は２人に１人と推測される。癌の種類は発生する部位や由来する細胞により様々であるため、癌の治療や予後予測には、それぞれの癌の浸潤・転移の能力を把握することが重要とされ、現在、国を挙げた包括的かつ効率的な対策が進められている。本研究において、低分子化合物ライブラリースクリーニングにより、乳癌に対する新規治療薬のシードを見つけた意義は学術的にも社会的にも大きいと言える。

Research Products

• [Int'l Joint Research] Qatar Biomedical Research Institute(カタール)
• [Int'l Joint Research] Chinese Academy of Sciences(中国)
• [Journal Article] The Potential Role of YAP in Axl-mediated Resistance to EGFR Tyrosine Kinase Inhibitors (2019)
  • Author(s): Saab S, Chang OS, Nagaoka K, Hung MC, Yamaguchi H
  • Journal Title: Am J Cancer Res Volume: 9 Pages: 2719-2729
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of a selective casein kinase 1δ and ε inhibitor on FcεRI expression and IgE-mediated immediate-type cutaneous reactions in dogs (2019)
  • Author(s): Ohno H, Takahashi K, Yanuma N, Ogawa M, Hasegawa A, Sugita K, Kawano K, Sasaki K, Shirai J, Nagaoka K, Ohmori K.
  • Journal Title: Journal of Veterinary Medical Science Volume: 81 Issue: 11 Pages: 1680-1684
  • DOI: 10.1292/jvms.18-0756
  • NAID: 130007757464
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] Fluvastatin Sodium Ameliorates Obesity through Brown Fat Activation. (2019)
  • Author(s): Yin N, Zhang H, Ye R, Dong M, Lin J, Zhou H, Huang Y, Chen L, Jiang X, Nagaoka K, Zhang C, Jin W
  • Journal Title: Int J Mol Sci Volume: 20 Issue: 7 Pages: 1622-1622
  • DOI: 10.3390/ijms20071622
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of membrane penetration and cytotoxicity of C9orf72-encoding arginine-rich dipeptides. (2018)
  • Author(s): Kanekura K, Harada Y, Fujimoto M, Yagi T, Hayamizu Y, Nagaoka K, Kuroda M
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 12740-12740
  • DOI: 10.1038/s41598-018-31096-z
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA detection at femtomolar concentrations with isothermal amplification and a biological nanopore (2017)
  • Author(s): Zhang Haolin、Hiratani Moe、Nagaoka Kentaro、Kawano Ryuji
  • Journal Title: Nanoscale Volume: 9 Issue: 42 Pages: 16124-16127
  • DOI: 10.1039/c7nr04215a
  • Peer Reviewed
• [Journal Article] Decrease of lactogenic hormones induce epithelial-mesenchymal transition via TGFβ1 and arachidonic acid during mammary gland involution (2017)
  • Author(s): Zhang H, Liu Y, Weng J, Usuda K, Fujii K, Watanabe G, Nagaoka K
  • Journal Title: Journal of Reproduction and Development Volume: 63 Issue: 3 Pages: 325-332
  • DOI: 10.1262/jrd.2016-157
  • NAID: 130007314609
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [Presentation] 細胞質ポリアデニル化複合体発現調節を介した乳がん抑制因子の探索 (2019)
  • Author(s): 石井由里子、Sovijit Warcharee、金蔵孝介、渡辺元、永岡謙太郎
  • Organizer: 日本分子生物学会
• [Presentation] Studies on posttranscriptional gene regulation in cancer progress (2018)
  • Author(s): Sovijit W, Nagaoka K, Watanabe G
  • Organizer: ASCB/EMBO 2018 meeting
  • Int'l Joint Research
• [Remarks] 東京農工大学獣医生理学研究室
  • URL: http://web.tuat.ac.jp/~nvetphys/