BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma.
BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma.
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DOI：
10.3390/ijms222111509
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发表时间：
2021-10-26
影响因子：
5.6
通讯作者：
Sato M
中科院分区：
文献类型：
--
作者：
Nagata T;Minami K;Yamamoto M;Hiraki T;Idogawa M;Fujimoto K;Kageyama S;Tabata K;Kawahara K;Ueda K;Ikeda R;Kato Y;Komatsu M;Tanimoto A;Furukawa T;Sato M
肺癌对人类健康构成威胁。BHLHE 41作为一种负调控转录因子，在生物节律和细胞分化中发挥重要作用。本研究探讨了BHLHE 41在肺癌进展中的作用。我们分析了BHLHE 41功能，通过在177例手术切除的非小细胞肺癌（NSCLC）样本和18例早期肺鳞状细胞癌（LUSC）病例的计算机和免疫组化研究。我们还研究了多西环素（DOX）诱导BHLHE 41表达A549和H2030腺癌细胞。BHLHE 41在正常肺组织中的表达高于肺腺癌（LUAD）组织，并与患者总生存期（OS）的预后较好相关。在132例LUAD组织中，共有15例在正常肺上皮细胞中表达BHLHE 41。染色主要见于原位腺癌和浸润性癌组织的片状生长部分。BHLHE 41表达是LUAD患者OS（p = 0.049）和病因特异性生存期（p = 0.042）的有利预后因素。在早期LUSC中，18例中有7例表达BHLHE 41，并且这种表达与浸润深度呈负相关。DOX抑制细胞增殖并增加自噬蛋白LC 3，而氯喹增强LC 3积累并抑制细胞死亡。在异种移植模型中，DOX抑制肿瘤生长。我们的研究结果表明，BHLHE41表达通过诱导NSCLC中的自噬细胞死亡来预防早期肺肿瘤恶性进展。
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.
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DOI：
10.1006/bbrc.2000.4133
发表时间：
2001-01-12
影响因子：
3.1
作者：
Fujimoto, K;Shen, M;Kato, Y
通讯作者：
Kato, Y
影响因子：
7.7
作者：
Gulbagci, Neriman Tuba;Li, Li;Taneja, Reshma
通讯作者：
Taneja, Reshma
影响因子：
20.4
作者：
Goldstraw, Peter;Chansky, Kari;Bolejack, Vanessa
通讯作者：
Bolejack, Vanessa
影响因子：
16.6
作者：
Bigot P;Colli LM;Machiela MJ;Jessop L;Myers TA;Carrouget J;Wagner S;Roberson D;Eymerit C;Henrion D;Chanock SJ
通讯作者：
Chanock SJ
DOI：
10.1097/pas.0000000000000134
发表时间：
2014-04
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kadota K;Villena-Vargas J;Yoshizawa A;Motoi N;Sima CS;Riely GJ;Rusch VW;Adusumilli PS;Travis WD
通讯作者：
Travis WD