Elucidation of three dimensional genome organization by Brd4 that confers cancer stemness

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15618
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: Yokoyama Yuhki 大阪大学, 医学系研究科, 助教 (60615714)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 三次元ゲノム構造 / エピジェネティクス / 大腸癌 / 癌幹細胞

Outline of Final Research Achievements

We initially planned to conduct study mainly using ovarian cancer cell lines, but the study using colorectal cancer cell lines progressed smoothly. Therefore, we focused on the study for colorectal cancer. In the first year, we found that the expression of cancer stem cell related genes were suppressed by the BET family protein inhibitor JQ1 in colorectal cancer as reported in ovarian cancer. We focused on the KLF5 gene, which has been reported as one of the cancer stem cell related gene, and preceded the study. As a result of analysis by the enChIP method, the enhancer candidate regions of the KLF5 gene were identified. In the second year, in situ Hi-C experiment was performed, and we found that the enhancer regions of the KLF5 gene may be located in the same TAD (topologically associating domain) as the KLF5 gene promoter region.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

癌幹細胞は腫瘍組織内に少数存在し、抗がん剤耐性や自己複製能、高い腫瘍形成能を持つことから、再発や転移の原因として考えられている。そのため、癌幹細胞を標的とした治療法の開発が望まれている。本研究の成果はKLF5遺伝子をはじめとした大腸癌の幹細胞関連遺伝子がBETファミリータンパクによって構築される三次元ゲノム構造を介して制御されている可能性を示すものであり、癌幹細胞を標的とした治療法の開発につながる可能性がある。