The mechanism of drug resistance regulated by miR-155 in T-ALL

• Project/Area Number: 15K19557
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: Koyama Daisuke 自治医科大学, 医学部, 客員研究員 (50741071)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: miR-155 / bortezomib / T-ALL / 薬剤耐性 / マイクロRNA / プロテアソーム阻害剤 / hsa-miR-155

Outline of Final Research Achievements

We previously reported that bortezomib induces cell death and increases chemosensitivity via transcriptional repression of Notch1 in T-cell acute lymphoblastic leukemia. The down-regulation of Notch1 was caused by the degradation of Sp1. But the mechanism of Sp1 degradation is still unknown. We hypothesized that Sp1 is degraded by some microRNA. In order to find the microRNA targeting Sp1, we performed the microRNA array and identified that miR-155 was up-regulated by bortezomib. We confirmed it using CRISPR/Cas9 system. These results indicated that miR-155 could be the biomarker of the drug sensitivity for bortezomib.

Research Products

• [Journal Article] Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma. (2015)
  • Author(s): Kikuchi J, Koyama D, Wada T, Izumi T, Hofgaad PO, Bogen B, Furukawa Y.
  • Journal Title: J Clin Invest Volume: 125 Issue: 12 Pages: 4375-4390
  • DOI: 10.1172/jci80325
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Overexpression of the shortest isoform of histone demethylase LSD1 primes hematopoietic stem cells for malignant transformation. (2015)
  • Author(s): Wada T, Koyama D, Kikuchi J, Honda H, Furukawa Y.
  • Journal Title: Blood Volume: 125 Issue: 24 Pages: 3731-3746
  • DOI: 10.1182/blood-2014-11-610907
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Soluble aKlotho as a Candidate for the Biomarker of Aging. (2015)
  • Author(s): Koyama, D., Sato, Y., Aizawa, M., Maki, T., Kurosawa, M., Kuro-o, M. and Furukawa, Y
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 467 Issue: 4 Pages: 1019-1025
  • DOI: 10.1016/j.bbrc.2015.10.018
  • Peer Reviewed
• [Remarks] 老化とくに骨粗鬆症の診断に有用な血中バイオマーカーの発見
  • URL: https://www.jichi.ac.jp/news/research/2015/20151124.html
• [Remarks] 老化とくに骨粗鬆症の診断に有用な血中バイオマーカーの発見
  • URL: http://www.jichi.ac.jp/openlab/newsletter/h46_spletter.pdf