BHLHE41/DEC2の発現は肺癌細胞の自食細胞死を誘導し、肺腺癌患者の良好な予後と関連している

• Material Type: 博士論文
• Title: BHLHE41/DEC2の発現は肺癌細胞の自食細胞死を誘導し、肺腺癌患者の良好な予後と関連している
• Author/Editor: 永田, 俊行
• Author Heading: 永田, 俊行 ナガタ, トシユキ
• Publication, Distribution, etc.: MDPI
• Alternative Title: BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma
• Degree grantor/type: 鹿児島大学
• Date Granted: 2022-05-30
• Dissertation Number: 甲総研第658号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: non-small cell lung cancer; BHLHE41; autophagic cell death; non-invasiveness
• Target Audience: 一般
• Note (General): 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨; Lung cancer constitutes a threat to human health. BHLHE41 plays important roles in circadian rhythm and cell differentiation as a negative regulatory transcription factor. This study investigates the role of BHLHE41 in lung cancer progression. We analyzed BHLHE41 function via in silico and immunohistochemical studies of 177 surgically resected non-small cell lung cancer (NSCLC) samples and 18 early lung squamous cell carcinoma (LUSC) cases. We also examined doxycycline (DOX)-inducible BHLHE41-expressing A549 and H2030 adenocarcinoma cells. BHLHE41 expression was higher in normal lung than in lung adenocarcinoma (LUAD) tissues and was associated with better prognosis for the overall survival (OS) of patients. In total, 15 of 132 LUAD tissues expressed BHLHE41 in normal lung epithelial cells. Staining was mainly observed in adenocarcinoma in situ and the lepidic growth part of invasive cancer tissue. BHLHE41 expression constituted a favorable prognostic factor for OS (p = 0.049) and cause-specific survival (p = 0.042) in patients with LUAD. During early LUSC, 7 of 18 cases expressed BHLHE41, and this expression was inversely correlated with the depth of invasion. DOX suppressed cell proliferation and increased the autophagy protein LC3, while chloroquine enhanced LC3 accumulation and suppressed cell death. In a xenograft model, DOX suppressed tumor growth. Our results indicate that BHLHE41 expression prevents early lung tumor malignant progression by inducing autophagic cell death in NSCLC. Toshiyuki Nagata, Kentaro Minami, Masatatsu Yamamoto, Tsubasa Hiraki, Masashi Idogawa, Katsumi Fujimoto, Shun Kageyama, Kazuhiro Tabata, Kohichi Kawahara, Kazuhiro Ueda, Ryuji Ikeda, Yukio Kato, Masaaki Komatsu, Akihide Tanimoto, Tatsuhiko Furukawa and Masami Sato BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma International Journal of Molecular Sciences 2021, 22, 11509 https://doi.org/10.3390/ijms222111509
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ

Table of Contents

Result_Nagata_toshiyuki_isk_658 other

Comments_Nagata_toshiyuki_isk_658 other

Diss_永田_俊行_ISK658_2022 fulltext

Abstract_永田_俊行_4511810126_2022 abstract