MICA expression regulation by small nucleic acids to prevent HCC occurrence

• Project/Area Number: 26460984
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Sato Masaya 東京大学, 医学部附属病院, 特任臨床医 (30722665)
• Co-Investigator(Kenkyū-buntansha): 大塚 基之 東京大学, 医学部附属病院, 助教 (90518945)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: MICA / 免疫療法 / 肝癌 / 自然免疫 / 癌 / NKG2D / NK細胞 / 核酸

Outline of Final Research Achievements

The investigators identified MICA gene as a susceptible gene to hepatocellular carcinoma by GWAS analyses using 1,394 HCV-related patients and 5,486 non-infected patients. In this study, MICA expression could be regulated by microRNA25-106b. Further, using CRISPR-Cas9 and Cas9-VP16 fusion construct, trascription of MICA mRNA could be augmented about te times. These results may lead to the regulation of MICA gene expression, which in turn result in the prevention of hepatocellular carcinoma occurrence.

Research Products

• [Int'l Joint Research] Icahn School of Medicine at Mount Sinai(米国)
• [Journal Article] Transcriptional activation of the MICA gene with an engineered CRISPR-Cas9 system (2017)
  • Author(s): Sekiba K, Yamagami M, Otsuka M, Suzuki T, Kishikawa T, Ishibashi R, Ohno M, Sato M, Koike K
  • Journal Title: Biochem Biophys Res Commun Volume: - Issue: 2 Pages: 521-525
  • DOI: 10.1016/j.bbrc.2017.03.076
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Development of a screening method to identify regulators of MICA shedding. (2015)
  • Author(s): Kishikawa T, Otsuka M, Ohno M, Yoshikawa T, Sato M, Koike K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 465 Issue: 4 Pages: 764-768
  • DOI: 10.1016/j.bbrc.2015.08.081
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ecreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine. (2015)
  • Author(s): Kishikawa T, Otsuka M, Tan PS, Ohno M, Sun X, Yoshikawa T, Shibata C, Takata A, Kojima K, Takehana K, Ohishi M, Ota S, Noyama T, Kondo Y, Sato M, Soga T, Hoshida Y, Koike K.
  • Journal Title: Oncotarget Volume: 6 Pages: 8339-8352
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Specific delivery of microRNA93 into HBV-replicating hepatocytes downregulates protein expression of liver cancer susceptible gene MICA. (2014)
  • Author(s): Ohno M, Otsuka M, Kishikawa T, Shibata C, Yoshikawa T, Takata A, Muroyama R, Kowatari N, Sato M, Kato N, Kuroda S, Koike K
  • Journal Title: Oncotarget Volume: 5 Pages: 5581-90
  • Peer Reviewed / Open Access / 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
• [Remarks] 研究グループホームページ
  • URL: https://sites.google.com/site/225kenncrna/