Zhang Qian, Guo Zhongliang
Shanghai East Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Department of Respiratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, P.R. China.
Oncol Lett. 2022 May 30;24(1):233. doi: 10.3892/ol.2022.13316. eCollection 2022 Jul.
As the most common type of lung cancer, lung adenocarcinoma (LUAD) poses a great threat to human health worldwide and severely compromises the quality of life of the patients. The present study aimed to explore the potential pathogenesis of LUAD. Reverse transcription-quantitative PCR and western blotting were applied to measure the expression levels of SEC61 translocon subunit γ (SEC61G) and cyclic AMP-responsive element-binding protein 3 (CREB3). Western blotting was also used to determine the expression of endoplasmic reticulum (ER) stress-, apoptosis- and migration-related proteins. Cell Counting Kit-8, colony formation, TUNEL, wound healing and Transwell assays were used, respectively, to determine the viability, proliferation, apoptosis, migration and invasion of LUAD A549 cells. The association between SEC61G and CREB3 was verified by co-immunoprecipitation assay. The results revealed that SEC61G was upregulated in A549 cells and its downregulation could activate ER stress. It was also found that silencing SEC61G inhibited the malignant development of LUAD through ER stress. In addition, SEC61G was verified to participate in ER stress in LUAD via CREB3 and silencing SEC61G exerted inhibitory effects on the malignant progression of LUAD by regulating CREB3. In summary, SEC61G participated in ER stress and its knockdown exerted inhibitory effects on A549 cells via regulating CREB3, which suggests that SEC61G may be a potential therapy for patients with LUAD.
作为最常见的肺癌类型，肺腺癌（LUAD）在全球范围内对人类健康构成了巨大威胁，并严重影响患者的生活质量。本研究旨在探讨LUAD的潜在发病机制。应用逆转录定量PCR和蛋白质印迹法检测SEC61转运体亚基γ（SEC61G）和环磷酸腺苷反应元件结合蛋白3（CREB3）的表达水平。蛋白质印迹法还用于测定内质网（ER）应激、凋亡和迁移相关蛋白的表达。分别采用细胞计数试剂盒-8、集落形成、TUNEL、伤口愈合和Transwell实验，来测定LUAD A549细胞的活力、增殖、凋亡、迁移和侵袭能力。通过免疫共沉淀实验验证SEC61G与CREB3之间的关联。结果显示，SEC61G在A549细胞中上调，其下调可激活内质网应激。还发现沉默SEC61G可通过内质网应激抑制LUAD的恶性发展。此外，证实SEC61G通过CREB3参与LUAD的内质网应激，沉默SEC61G通过调节CREB3对LUAD的恶性进展产生抑制作用。总之，SEC61G参与内质网应激，其敲低通过调节CREB3对A549细胞产生抑制作用，这表明SEC61G可能是LUAD患者的一种潜在治疗靶点。
