Analysis of aberrant microRNA expression due to the type of fusion gene in Ewing's sarcoma.

• Project/Area Number: 17K10971
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Oita University
• Principal Investigator: Kawano Masanori 大分大学, 医学部, 助教 (30571773)
• Co-Investigator(Kenkyū-buntansha): 田仲 和宏 大分大学, 医学部, 准教授 (10274458)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Ewing肉腫 / マイクロRNA / EWS-Fli1 / miRNA / ユーイング肉腫 / 融合遺伝子 / 癌 / マイクロアレイ

Outline of Final Research Achievements

Ewing sarcoma, a typical primary bone tumor, commonly develops in children and young adults, is highly malignant and has a poor prognosis, so we are awaiting development of new treatment methods. In Ewing sarcoma, the central component of the carcinogenesis mechanism is EWS-Fli1 working as an abnormal transcription factor, which requires a completely different treatment approach to conventional cancers. We will extract factors that increase or decrease across different subtypes, while simultaneously identifying factors where the expression changes do not match between subtypes, using the miRNA and mRNA extracted after EWS-Fli1 knock down. Through this research we plan to not only elucidate the carcinogenic mechanism of Ewing sarcoma, but also identify prognostic factors by EWS-Fli1 type, which we hope will lead to discovery of biomarkers and development of individualized treatment.

Academic Significance and Societal Importance of the Research Achievements

本研究により、type別にその下流遺伝子発現がどのように変化するのかを突き止めることが可能となる。EWS-Fli1に制御されEwing肉腫のがん化に寄与する因子、type 2の予後を悪化させる特異的な因子を同定、それらの生物学的意義を検証し、臨床応用への道を拓くことが期待できる。

Research Products

• [Journal Article] A meta-analysis of randomized controlled trials that compare standard doxorubicin with other first-line chemotherapies for advanced/metastatic soft tissue sarcomas. (2019)
  • Author(s): Tanaka K, Kawano M, Iwasaki T, Itonaga I, Tsumura H.
  • Journal Title: PLoS One. Volume: 14 Pages: 1-18
  • DOI: 10.1371/journal.pone.0210671
  • Peer Reviewed / Open Access
• [Journal Article] Surrogacy of intermediate endpoints for overall survival in randomized controlled trials of first-line treatment for advanced soft tissue sarcoma in the pre- and post-pazopanib era: a meta-analytic evaluation. (2019)
  • Author(s): Tanaka K, Kawano M, Iwasaki T, Itonaga I, Tsumura H.
  • Journal Title: BMC Cancer Volume: 19 Pages: 56-56
  • DOI: 10.1186/s12885-019-5268-2
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing's sarcoma cells. (2018)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
  • Journal Title: Cancer Cell International Volume: 18 Pages: 1-11
  • DOI: 10.1186/s12935-018-0536-9
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-20b promotes cell proliferation via targeting of TGF-β receptor II and upregulates MYC expression in Ewing's sarcoma cells. (2018)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
  • Journal Title: Int J Oncol Volume: 51(6) Pages: 1842-1850
  • DOI: 10.3892/ijo.2017.4155
  • Peer Reviewed / Open Access
• [Journal Article] Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment. (2018)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H.
  • Journal Title: Cell Communication and Signaling Volume: 16(1) Pages: 1-11
  • DOI: 10.1186/s12964-018-0225-2
  • Peer Reviewed / Open Access