Functional analysis of circ/miRNA in malignant lymphoma

• Project/Area Number: 17K09914
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Akita University
• Principal Investigator: TAGAWA HIROYUKI 秋田大学, 医学系研究科, 非常勤講師 (30373492)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: circRNA / malignant lymphoma / circ-MTO1 / miRNA / 13q31 / miR-17 / circMTO1 / B cell lymphoma / miR-20 / PTEN / miR-26 / invasion / multiple myeloma / 悪性リンパ腫 / 血液腫瘍学 / 内科学

Outline of Final Research Achievements

Circular RNA is a circular non-coding RNA that adsorbs miRNA to complementary sequences and causes abnormal expression. We identified several circRNA candidates required for tumor cell maintenance, examined changes in their downstream miRNAs, and identified circ-MTO1 as a circRNA whose expression is reduced in B-cell lymphoma. circ-MTO1 adsorbs the oncogenes miR-17 and miR-20. Therefore, It was speculated that the decreased expression of the circRNA causes an abnormal increase in the expression of miR-17 and miR-20, with the expression of the tumor suppressor gene PTEN, which is the target protein of these miRNAs.

Academic Significance and Societal Importance of the Research Achievements

我々の研究はcircRNAのがん生物学的な意義を初めて明らかにする試みであり、がんとcircRNAに関する新分野を開拓できる。そのことにより従来の解析法では一部未知であったリンパ腫をはじめとするがんの病態解明に大きな前進を与える。本研究課題は、新しい治療法や診断法の開発のシーズとして産業的、経済的に大きな潜在性を有しており、また機序の解明は社会的に大きなインパクトを与えることができる。

Research Products

• [Journal Article] Hypoxia-inducible KDM3A addiction in multiple myeloma. (2018)
  • Author(s): Ikeda S, Kitadate A, Abe F, Takahashi N, Tagawa H.
  • Journal Title: Blood Advances Volume: 2(4) Issue: 4 Pages: 323-334
  • DOI: 10.1182/bloodadvances.2017008847
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Histone deacetylase inhibitors downregulate CCR4 expression and decrease mogamulizumab efficacy in CCR4-positive mature T-cell lymphomas. (2018)
  • Author(s): Kitadate A, Ikeda S, Abe F, Takahashi N, Shimizu N, Matsue K, Tagawa H.
  • Journal Title: Haematologica Volume: 103(1) Issue: 1 Pages: 126-135
  • DOI: 10.3324/haematol.2017.177279
  • Peer Reviewed / Open Access
• [Journal Article] A distinct subtype of Epstein Barr virus positive T/NK-cell lymphoproliferative disorder: Adult patients with chronic active Epstein Barr virus infection-like features. (2018)
  • Author(s): Kawamoto K, Miyoshi H, Suzuki T, Kozai Y, Kato K, Miyahara M, Yujiri T, Oishi N, Choi I, Fujimaki K, Muta T, Kume M, Moriguchi S, Tamura S, Kato T, Tagawa H, Makiyama J, Kanisawa Y, Sasaki Y, Kurita D, Yamada K, Shimono J, Sone H, Takizawa J, Seto M, Kimura H, Ohshima K.
  • Journal Title: Haematologica Volume: 未定
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia-inducible microRNA-210 regulates the DIMT1-IRF4 oncogenic axis in multiple myeloma. (2017)
  • Author(s): Ikeda S, Kitadate A, Abe F, Saitoh H, Michishita Y, Hatano Y, Kawabata Y, Kitabayashi A, Teshima K, Kume M, Takahashi N, Tagawa H.
  • Journal Title: Cancer Science Volume: 108(4) Issue: 4 Pages: 641-652
  • DOI: 10.1111/cas.13183
  • Peer Reviewed / Open Access
• [Presentation] Role of miRNA in malignant lymphoma (2017)
  • Author(s): Tagawa Hiroyuki
  • Organizer: アジア太平洋がん学会(APCC in Soul)
  • Int'l Joint Research / Invited