Inflammation -associated colon carcinogenesis by microRNA functional impairment

• Project/Area Number: 16K19329
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: YOSHIKAWA Takeshi 東京大学, 医学部附属病院, 特任臨床医 (40631685)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: microRNA / 炎症発癌 / 炎症性発癌 / 発癌 / 慢性炎症 / 炎症続発性腫瘍

Outline of Final Research Achievements

The biological significances of microRNA functional impairment during chronic inflammation was determined. When Dicer protein is decreased at about half level, it resulted in the higher possibilities of carcinogenesis. To discover the underlying molecular mechanisms, tetracyclin-regulated Dicer expressing cells were established, and using these cells it was found that CEB/P pathway is crucial in the inflammatory-tumorigenesis.ROCK inhibitor reverses these effects. Thus, ROCK inhibitor may be useful for the prevention of inflammation-associated tumorigenesis.

Academic Significance and Societal Importance of the Research Achievements

慢性炎症に続発する腫瘍は様々な臓器組織で見られるので、この制御は重要な課題である。炎症によってmicroRNA機能が減弱することが腫瘍形成に大きくかかわっていることが示唆されていたが、そのメカニズムとしてCEB/P経路が重要であることを見出した。また、microRNA機能を増強する作用を持つROCK阻害剤を用いると、慢性炎症に続発する腫瘍形成を抑制することが出来ることを見出し、今後の炎症続発性腫瘍の予防法として有用であることが示唆された。

Research Products

• [Journal Article] Repression of miRNA function mediates inflammation-associated colon tumorigenesis. (2017)
  • Author(s): Yoshikawa T., J. F. Wu, M. Otsuka, T. Kishikawa, N. Suzuki, A. Takata, M. Ohno, R. Ishibashi, M. Yamagami, R. Nakagawa, N. Kato, M. Miyazawa, J. Han, and K. Koike
  • Journal Title: Gastroenterology Volume: 152 Issue: 3 Pages: 631-643
  • DOI: 10.1053/j.gastro.2016.10.043
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant