Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, P.R. China.
Department of Respiratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, P.R. China.
Oncol Rep. 2021 Mar;45(3):1226-1234. doi: 10.3892/or.2020.7913. Epub 2020 Dec 30.
Obstructive sleep apnea (OSA) is a sleep‑related disorder characterized by chronic intermittent hypoxia (CIH). Previous studies have found that intermittent hypoxia promotes drug resistance, cell proliferation, migration and invasion in non‑small cell lung cancer (NSCLC). Endothelial cell‑specific molecule‑1 (ESM1) is a molecule shown to be overexpressed in several types of tumors. The purpose of this study was to investigate the correlation between CIH and ESM1 and their potential roles in the progression of NSCLC. Tumorspheres, cell viability and colony formation assays were used to evaluate cell proliferation. The expression levels of cancer stem cell (CSC) markers CD44, CD133, OCT4 and SOX2 were measured with western blotting and/or RT‑qPCR. Transwell assays were applied to assess cell migration and invasion. Changes in the expression levels of epithelial‑mesenchymal transition (EMT)‑associated proteins were also detected by western blotting. The results indicated that CIH enhanced lung cancer stem cell (LCSC) NSCLC progression by promoting stemness, drug resistance, cell proliferation, migration and invasion via the ESM1/HIF‑1α pathway. Unexpectedly, inhibition of ESM1 reversed the CIH‑involved negative effects on LCSCs and in a mouse model. ESM1 therefore appears to be crucial mediator of CIH‑mediated lung cancer progression.
阻塞性睡眠呼吸暂停（OSA）是一种与睡眠相关的疾病，其特征为慢性间歇性低氧（CIH）。先前的研究发现，间歇性低氧会促进非小细胞肺癌（NSCLC）中的耐药性、细胞增殖、迁移和侵袭。内皮细胞特异性分子-1（ESM1）是一种在多种类型的肿瘤中表达过高的分子。本研究旨在探讨 CIH 与 ESM1 之间的相关性及其在 NSCLC 进展中的潜在作用。肿瘤球体形成、细胞活力和集落形成实验用于评估细胞增殖。通过 Western blot 和/或 RT-qPCR 测量癌症干细胞（CSC）标志物 CD44、CD133、OCT4 和 SOX2 的表达水平。Transwell 实验用于评估细胞迁移和侵袭。通过 Western blot 检测上皮-间充质转化（EMT）相关蛋白表达水平的变化。结果表明，CIH 通过 ESM1/HIF-1α 通路增强了肺癌干细胞（LCSC）的 NSCLC 进展，促进了干性、耐药性、细胞增殖、迁移和侵袭。出乎意料的是，ESM1 的抑制作用逆转了 CIH 对 LCSC 的不利影响，并在小鼠模型中得到了验证。因此，ESM1 似乎是 CIH 介导的肺癌进展的关键介质。
