Researching that global repression of miRNA function may cause inflammation-associated gastric and hepatic tumorigenesis

• Project/Area Number: 25860520
• 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): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: microRNA / 炎症性発癌 / 肝癌

Outline of Final Research Achievements

I am researching "chronic impairment of microRNA function due to chronic inflammation may cause inflammation-associated tumorigenesis" and "preventing
inflammation-associated tumorigenesis". I published that ROCK inhibitor enhanced remaining miRNA function by promoting miRNA-mediated mRNA decay. And I am submitting the paper that global impairment of miRNA function in chronic inflammation may have a causal role in inflammation-associated colonic oncogenesis, and enhancement of miRNA function is a potential method for preventing colonic inflammation-associated tumorigenesis. This time I researched gastric and hepatic inflammation-associated tumorigenesis, but enhancement of miRNA function did not prevent inflammation-associated tumorigenesis of stomach and liver. Hereafter I will research molecular mechanism that global impairment of miRNA function contribute to inflammation-associated oncogenesis.

Research Products

• [Journal Article] ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression (2015)
  • Author(s): Yoshikawa, T. Wu, J. Otsuka, M. Kishikawa, T. Ohno, M. Shibata, C. Takata, A. Han, F. Kang, Y. J. Chen, C. A. Shyu, A. B. Han, J. Koike, K
  • Journal Title: Nucleic Acids Res Volume: 43(15) Issue: 15 Pages: 7577-89
  • DOI: 10.1093/nar/gkv728
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The role of microRNAs in hepatocarcinogenesis: current knowledge and future prospects. (2014)
  • Author(s): Otsuka M, Kishikawa T, Yoshikawa T, Ohno M, Takata A, Shibata C, Koike K.
  • Journal Title: J Gastroenterol. Volume: 49 Issue: 2 Pages: 173-84
  • DOI: 10.1007/s00535-013-0909-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model. (2013)
  • Author(s): Yoshikawa T, Otsuka M, Kishikawa T, Takata A, Ohno M, Shibata C, Kang YJ, Yoshida H, Koike K.
  • Journal Title: PLoS One. Volume: 8(9) Issue: 9 Pages: e71969-e71969
  • DOI: 10.1371/journal.pone.0071969
  • Peer Reviewed
• [Presentation] Enhancing microRNA function may prevent colon carcinogenesis (2014)
  • Author(s): Yoshikawa T, Otsuka M, Koike K
  • Organizer: JDDW 2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23 – 2014-10-26
• [Presentation] 慢性炎症に伴う大腸腫瘍発生におけるDicer遺伝子の特殊な癌抑制作用の解明 (2014)
  • Author(s): 吉川剛史 大塚基之 小池和彦
  • Organizer: 第100回 日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-23 – 2014-04-26
• [Presentation] Obligate haploinsufficiency of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model (2014)
  • Author(s): Yoshikawa T, Otsuka M, Koike K
  • Organizer: American Association for Cancer Research 2014
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Obligate haploinsufficiency of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model (2014)
  • Author(s): Yoshikawa T, Otsuka M, Koike K
  • Organizer: American Association for Cancer Research 2014
  • Place of Presentation: Sandiego, USA
• [Presentation] Functional impairment of microRNAs induced by chronic inflammation is the cause of inflammation-associated colon tumorigenesis (2013)
  • Author(s): Yoshikawa T, Otsuka M, Koike K
  • Organizer: American Association for Cancer Research 2013
  • Place of Presentation: Washington, DC, USA