An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16440
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kanazawa University (2022); Osaka University (2020-2021)
• Principal Investigator: Horie Masafumi 金沢大学, 医学系, 准教授 (60732659)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ELF3 / ATAC-seq / CUT&Tag / スーパーエンハンサー / ASCL1

Outline of Final Research Achievements

Using 3 ELF3 high-expression cell lines, we conducted open chromatin analysis by ATAC-seq and comprehensive histone modification analysis by CUT&Tag. We discovered that ELF3 functions as a super-enhancer-associated transcription factor in ASCL1-type small cell lung cancer (SCLC). Furthermore, we performed CUT&Tag using anti-ELF3 antibody and KD-RNA-seq using siRNA to list the target genes of ELF3. Pathway analysis of the ELF3-target genes suggested their involvement in cell survival and the cell cycle, which was confirmed by cell proliferation assays and cell cycle analysis using siRNA.

Free Research Field

肺小細胞癌

Academic Significance and Societal Importance of the Research Achievements

ELF3はASCL1型のSCLCではスーパーエンハンサー関連転因子として腫瘍促進的な役割を果たすことが示された。ELF3は膀胱癌や十二指腸癌ではがん抑制遺伝子として働いており、がん抑制促進の２面性を持つcontext-dependentな転写因子であることが本研究により明らかになった。