Elucidating the mechanism of TWIST1 contribution to OA using genome-wide enhancer analysis

Research Project

Project/Area Number	18K09065
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56020:Orthopedics-related
Research Institution	Okayama University
Principal Investigator	Hasei Joe 岡山大学, 医学部, 客員研究員 (40636213)
Co-Investigator(Kenkyū-buntansha)	寺村岳士近畿大学, 大学病院, 講師 (40460901) 村川泰裕国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50765469)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	TWIST1 / 転写因子 / エンハンサー / ゲノムワイド
Outline of Final Research Achievements	Transcriptome and NET-CAGE analyses of TWIST1-expressing cells revealed that TWIST1 expression correlated with the expression of stemness/undifferentiability-related genes such as ID1, ID2, and Bmi1. Therefore, we reanalyzed RNAseq and microarray data to identify cell surface markers that are highly correlated with TWIST1 expression. We found that TWIST1 strongly correlated with the cell surface protein LRRC15. Currently, development of ADC drugs targeting LRRC15 is underway, and the results of this study support the validity of LRRC15 as a therapeutic target.
Academic Significance and Societal Importance of the Research Achievements	TWIST1は軟骨だけでなく、発生や、腫瘍などにおいて広く重要な働きをしている転写因子である。本研究結果は、TWIST1が関わる重要な転写因子として働きの新たな一部を解明する手がかりになるものであり、今後、がん研究分野においてもつながるものであった。