Circadian rhythm disruption in human cancers

• Project/Area Number: 25860179
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yasuhiro Umemura 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40612734)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 体内時計 / がん / 細胞分化 / 概日時計

Outline of Final Research Achievements

To elucidate the correlation between circadian clock development and differentiation stage of cancer cells, the circadian clock in the several human cancer cell lines were investigated. The circadian clock rhythm of these human cancer cell lines was not detected. However, the clock gene set in these cell lines was expressed. Next, the model of cancer development cell lines by myc overexpression using mouse embryonic stem cells (ESCs) was established. The in vitro differentiated ES cells during the induction of myc showed no circadian rhythm oscillation. The global gene expression analysis by RNA-seq identified the gene network inhibiting clock formation.

Research Products

• [Journal Article] Parathyroid hormone resets the cartilage circadian clock of the organ-cultured murine femur. (2015)
  • Author(s): Okubo N, Fujiwara H, Minami Y, Kunimoto T, Hosokawa T, Umemura Y, Inokawa H, Asada M, Oda R, Kubo T, Yagita K.
  • Journal Title: Acta Orthopedica Volume: 13 Issue: 5 Pages: 1-5
  • DOI: 10.3109/17453674.2015.1029393
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transcriptional Program of Kpna2 /Importin-α2 Regulates Cellular Differentiation-Coupled Circadian Clock Development in Mammalian Cells. (2014)
  • Author(s): Umemura Y, Koike N, Matsumoto T, Yoo S-H, Zhen C, Yasuhara N, Takahashi JS, Yagita K.
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Issue: 47 Pages: 5039-48
  • DOI: 10.1073/pnas.1419272111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cell and Tissue-autonomous development of the circadian clock in mouse embryos. (2014)
  • Author(s): Inada Y, Uchida H, Umemura Y, Nakamura W, Sakai T, Koike N, Yagita K.
  • Journal Title: FEBS Lett Volume: 588 Issue: 3 Pages: 459-465
  • DOI: 10.1016/j.febslet.2013.12.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prolonged Bioluminescence Monitoring in Mouse ex vivo Bone Culture Revealed Persistent Circadian Rhythms in Articular Cartilages and Growth Plates. (2013)
  • Author(s): Okubo N, Minami Y, Fujiwara H, Umemura Y, Tsuchiya Y, Shirai Y, Oda R, Inokawa H, Kubo T, Yagita K*.
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e78306-e78306
  • DOI: 10.1371/journal.pone.0078306
  • Peer Reviewed
• [Presentation] 発生過程における概日時計の成立機構の解明 (2015)
  • Author(s): 八木田和弘, 小池宣也, 梅村康浩、大橋宗洋
  • Organizer: 新学術領域研究「ゲノム支援」
  • Place of Presentation: 京都
  • Year and Date: 2015-08-27
• [Presentation] 細胞分化センサーとしての生物時計 (2014)
  • Author(s): 梅村康浩
  • Organizer: 細胞センサーの分子機構・相互関連・ネットワーク研究会
  • Place of Presentation: 愛知、岡崎
  • Year and Date: 2014-12-04
• [Presentation] 細胞分化に伴う哺乳類概日時計の発生分子メカニズム (2014)
  • Author(s): 梅村康浩, 小池宣也, 安原徳子, 八木田和弘
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-17 – 2014-10-18
• [Presentation] An in vitro ES cell-based clock recapitulation assay model identifies CK2alpha as an endogenous clock regulator. (2013)
  • Author(s): Umemura Y, Yoshida J, Wada M, Tsuchiya Y, Minami Y, Watanabe H, Kondoh G, Takeda J, Inokawa H, Horie K, Yagita K
  • Organizer: 第８６回日本生化学大会
  • Place of Presentation: 横浜
• [Book] 細胞工学 2015年３月号 (2015)
  • Author(s): 梅村康浩, 八木田和弘
  • Total Pages: 2
  • Publisher: 株式会社 学研メディカル秀潤社