{"title":"HSPE1 可增强有氧糖酵解，促进肺腺癌的进展","authors":"Tao Xie , Manxiang Li","doi":"10.1016/j.mrfmmm.2024.111867","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to explore the role of heat shock protein family E member 1 (HSPE1) in the metabolism of lung adenocarcinoma (LUAD) cells.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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 <em>in vivo</em>.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111867"},"PeriodicalIF":1.5000,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HSPE1 enhances aerobic glycolysis to promote progression of lung adenocarcinoma\",\"authors\":\"Tao Xie , Manxiang Li\",\"doi\":\"10.1016/j.mrfmmm.2024.111867\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>This study aimed to explore the role of heat shock protein family E member 1 (HSPE1) in the metabolism of lung adenocarcinoma (LUAD) cells.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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 <em>in vivo</em>.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":49790,\"journal\":{\"name\":\"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis\",\"volume\":\"829 \",\"pages\":\"Article 111867\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-06-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0027510724000174\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0027510724000174","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
HSPE1 enhances aerobic glycolysis to promote progression of lung adenocarcinoma
Objective
This study aimed to explore the role of heat shock protein family E member 1 (HSPE1) in the metabolism of lung adenocarcinoma (LUAD) cells.
Methods
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.
Results
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.
Conclusion
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.
期刊介绍：
Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs.
MR publishes articles in the following areas:
Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence.
The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance.
Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing.
Landscape of somatic mutations and epimutations in cancer and aging.
Role of de novo mutations in human disease and aging; mutations in population genomics.
Interactions between mutations and epimutations.
The role of epimutations in chromatin structure and function.
Mitochondrial DNA mutations and their consequences in terms of human disease and aging.
Novel ways to generate mutations and epimutations in cell lines and animal models.
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