Mechanism of clonal evolution by both CUX1 and miR-145 haploinsufficiency

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07637
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: University of Fukui
• Principal Investigator: Hosono Naoko 福井大学, 学術研究院医学系部門(附属病院部), 講師 (50509312)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 7番染色体 / CUX1 / ハプロ不全 / miR-145 / TGF-β

Outline of Final Research Achievements

Using an acute myeloid leukemia cell line (HL60), we generated a cell line with low expression of both the CUX1 gene and microRNA-145, which are presumed to be involved in the mechanism of tumorigenesis. In HL60 cells with normal CUX1 expression (parental line), TGFβ inhibitor treatment induced cell proliferation and attenuated the effect of anticancer drugs used to treat leukemia. This indicates that the expression level of TGFβ is involved in the cell proliferation and cell death in myeloid leukemia cells. Detailed evaluation of DNA repair mechanisms is currently underway.

Free Research Field

造血器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

様々な悪性腫瘍において、Transforming growth factor-β(TGF-β)は、腫瘍増殖因子として知られているが、急性骨髄性白血病細胞株を用いた検討では、TGF-βの作用を阻害すると腫瘍細胞が増殖をきたし、抗がん剤にも抵抗性を示すという、TGF-βの相反する作用がうかがえる結果であった。TGF-βが白血病細胞の腫瘍進展のみならず、治療抵抗性のメカニズムにも関与する可能性が示唆され、白血病細胞に高率に欠損する転写因子であるCUX1の発現低下時における腫瘍化の病態解明に新たな一歩を示す研究成果である。