2022 Fiscal Year Final Research Report

Multilateral analysis of the regulatory mechanism of transcription factor BHLHE41/DEC2 expression and its clinical significance in lung cancer.

Research Project

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Project/Area Number	20K09181
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55040:Respiratory surgery-related
Research Institution	Kagoshima University (2022) Shizuoka Cancer Center Research Institute (2020-2021)
Principal Investigator	NAGATA Toshiyuki 鹿児島大学, 医歯学域医学系, 助教 (70611763)
Co-Investigator(Kenkyū-buntansha)	佐藤雅美鹿児島大学, 医歯学域医学系, 教授 (30250830) 上田和弘鹿児島大学, 医歯学総合研究科, 特任准教授 (90420520) 狩集弘太鹿児島大学, 医歯学域鹿児島大学病院, 助教 (20648050) 横枕直哉鹿児島大学, 医学部・歯学部附属病院, 助教 (00418857) 前田光喜鹿児島大学, 医歯学域鹿児島大学病院, 助教 (70795674) 武田亜矢鹿児島大学, 医歯学総合研究科, 特任助教 (80794700) 梅原正鹿児島大学, 医歯学域鹿児島大学病院, 助教 (20837794) 上村豪鹿児島大学, 医歯学域鹿児島大学病院, 助教 (80927187)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	BHLHE41/DEC2 / 肺癌 / オートファジー
Outline of Final Research Achievements	The purpose of this study was to clarify the regulatory mechanism and role of BHLHE41/DEC2 expression in non-small cell lung cancer, and to examine its application to early diagnosis and potential as a therapeutic target. First, both in vitro experiments using lung cancer cell lines and in vivo experiments using immunodeficient mice showed that increased expression of BHLHE41/DEC2 suppressed tumor cell growth. Next, to elucidate the mechanism by which DEC2 expression suppresses tumor growth, we examined the relationship with apoptosis, but found that it was not significantly involved. We found that autophagy is induced by BHLHE41/DEC2 expression in lung cancer cells based on Autophagy flux assay and Fluorescence Associated with ftLC3 Expression, and elucidated part of the mechanism.
Free Research Field	呼吸器外科
Academic Significance and Societal Importance of the Research Achievements	BHLHE41/DEC2の発現制御機構に関して、アポトーシスが大きく関与しておらず、BHLHE41/DEC2の発現によりオートファジーが誘導されるとの結果を得、機序の一端を解明した。更に、肺癌進行過程の早期と中・後期ではBHLHE41/DEC2の発現が異なることが確認され、肺癌における悪性化進行過程を考慮したオートファジー研究につながる可能性を秘めた結果であった。