Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi 'an Jiaotong University, Xi 'an 710061, China; Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Infammation and Allergic Diseases Research Unit, The Afliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi 'an Jiaotong University, Xi 'an 710061, China.
Mutat Res. 2024 Jul-Dec;829:111867. doi: 10.1016/j.mrfmmm.2024.111867. Epub 2024 Jun 8.
This study aimed to explore the role of heat shock protein family E member 1 (HSPE1) in the metabolism of lung adenocarcinoma (LUAD) cells.
Bioinformatics analysis was applied to examine the expression of HSPE1 in LUAD and its correlation with patient survival. Single-gene Gene Set Enrichment Analysis was conducted for HSPE1. LUAD cell lines or mouse models with up-regulated/down-regulated HSPE1 were constructed. The expression level of HSPE1 was detected by qRT-PCR or immunohistochemical staining. We used CCK-8 assay to measure cell viability and flow cytometry to detect apoptosis levels. Transwell assay was performed to evaluate migration and invasion characteristics. Extracellular Flux Analyzer was employed to detect oxygen consumption rate and extracellular acidification rate. Glucose consumption, adenosine triphosphate production, and lactate levels were measured by Reagent kits. Western blot analysis was conducted to examine the expression levels of GLUT1, HK2, and LDHA.
HSPE1 promoted proliferative, migratory, and invasive abilities, and inhibited apoptosis of LUAD cells through the aerobic glycolysis pathway. Specifically, LUAD cells with HSPE1 knockdown exhibited significantly decreased proliferation, migration, and invasion abilities, along with an increased apoptosis rate. Additionally, the expression levels of aerobic glycolysis-related proteins HK2, LADH, and GLUT1 were downregulated, while their levels were increased in LUAD cells with high HSPE1 expression. Suppression of aerobic glycolysis by 2-DG attenuated the promoting effects of HSPE1 overexpression on the proliferation, migration, and invasion of LUAD cells. HSPE1 knockdown inhibited tumor growth and decreased expression levels of HK2, LADH, and GLUT1 in vivo.
HSPE1 regulated the proliferation, migration, and invasion of LUAD cells through the aerobic glycolysis pathway, thus facilitating malignant development of LUAD. The study suggested that HSPE1 could be useful as a therapeutic target for LUAD.
本研究旨在探讨热休克蛋白家族 E 成员 1（HSPE1）在肺腺癌（LUAD）细胞代谢中的作用。
应用生物信息学分析方法检测 HSPE1 在 LUAD 中的表达及其与患者生存的相关性。对 HSPE1 进行单基因基因集富集分析。构建 HSPE1 上调/下调的 LUAD 细胞系或小鼠模型。采用 qRT-PCR 或免疫组化染色检测 HSPE1 的表达水平。用 CCK-8 法检测细胞活力，用流式细胞术检测细胞凋亡水平。Transwell 实验检测细胞迁移和侵袭特性。用外通量分析仪检测耗氧率和细胞外酸化率。用试剂盒检测葡萄糖消耗、三磷酸腺苷（ATP）生成和乳酸水平。用 Western blot 分析检测 GLUT1、HK2 和 LDHA 的表达水平。
HSPE1 通过有氧糖酵解途径促进 LUAD 细胞的增殖、迁移和侵袭能力，并抑制细胞凋亡。具体来说，HSPE1 敲低的 LUAD 细胞增殖、迁移和侵袭能力明显下降，凋亡率增加。此外，有氧糖酵解相关蛋白 HK2、LADH 和 GLUT1 的表达水平下调，而 HSPE1 高表达的 LUAD 细胞中其表达水平增加。2-DG 抑制有氧糖酵解减弱了 HSPE1 过表达对 LUAD 细胞增殖、迁移和侵袭的促进作用。HSPE1 敲低抑制肿瘤生长，降低体内 HK2、LADH 和 GLUT1 的表达水平。
HSPE1 通过有氧糖酵解途径调节 LUAD 细胞的增殖、迁移和侵袭，从而促进 LUAD 的恶性发展。该研究表明，HSPE1 可能是 LUAD 的一个有治疗价值的靶点。
