{"title":"骨质疏松症中内质网应激相关基因的生物信息学分析和实验验证","authors":"Yong Zheng, Yonggui Luo, Kuihan Tang","doi":"10.2147/IJGM.S486776","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Endoplasmic reticulum stress (ERS) is closely associated with Osteoporosis (OP). In order to explore the role of ERS related genes in OP and its molecular mechanism.</p><p><strong>Methods: </strong>OP-related transcriptome data were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to screen OP-related genes. Differentially expressed ERS-related genes (DE-ERSGs) between OP and controls were identified by overlapping OP-related, differentially expressed genes (DEGs), and ERS-related genes. ERS-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore their functions. Receiver operating characteristic (ROC) curves assessed the diagnostic value of DE-ERSGs, and comparative toxicogenomics database (CTD) was used to predict targeting agents for key DE-ERSGs. Finally, biomarker expression was verified by real time quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>A total of 10 DE-ERSGs were screened in OP patients. GO and KEGG analyses indicated their enrichment in Alcoholic liver disease, Endometrial cancer, and Glycerolipid metabolism. ROC curve analysis revealed that RPN2, FOXO3, ERGIC2, and MYO9A had significant diagnostic value, thus being identified as key DE-ERSGs. Moreover, the key DE-ERSGs-drug interaction network showed that some drugs such as bisphenol A, Cisplatin, Cyclosporine, and Valproic Acid might play roles by targeting key DE-ERSGs in OP. The expression validation analysis of key DE-ERSGs revealed that RPN2, ERGIC2, and MYO9A was significantly expressed in the GSE62402. Ultimately, The blood samples RT-qPCR verification results show that RPN2, ERGIC2, and MYO9A were significantly lower in OP samples compared to normal samples (p < 0.05), whereas there was no difference in the expression levels of FOXO3.</p><p><strong>Conclusion: </strong>RPN2, FOXO3, ERGIC2 and MYO9A as the biomarkers associated with ERS in OP by bioinformatics analysis, which may provide new biological targets for clinical treatment.</p>","PeriodicalId":14131,"journal":{"name":"International Journal of General Medicine","volume":"17 ","pages":"5359-5371"},"PeriodicalIF":2.1000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583764/pdf/","citationCount":"0","resultStr":"{\"title\":\"Bioinformatics Analysis and Experimental Validation of Endoplasmic Reticulum Stress-Related Genes in Osteoporosis.\",\"authors\":\"Yong Zheng, Yonggui Luo, Kuihan Tang\",\"doi\":\"10.2147/IJGM.S486776\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Endoplasmic reticulum stress (ERS) is closely associated with Osteoporosis (OP). In order to explore the role of ERS related genes in OP and its molecular mechanism.</p><p><strong>Methods: </strong>OP-related transcriptome data were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to screen OP-related genes. Differentially expressed ERS-related genes (DE-ERSGs) between OP and controls were identified by overlapping OP-related, differentially expressed genes (DEGs), and ERS-related genes. ERS-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore their functions. Receiver operating characteristic (ROC) curves assessed the diagnostic value of DE-ERSGs, and comparative toxicogenomics database (CTD) was used to predict targeting agents for key DE-ERSGs. Finally, biomarker expression was verified by real time quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>A total of 10 DE-ERSGs were screened in OP patients. GO and KEGG analyses indicated their enrichment in Alcoholic liver disease, Endometrial cancer, and Glycerolipid metabolism. ROC curve analysis revealed that RPN2, FOXO3, ERGIC2, and MYO9A had significant diagnostic value, thus being identified as key DE-ERSGs. Moreover, the key DE-ERSGs-drug interaction network showed that some drugs such as bisphenol A, Cisplatin, Cyclosporine, and Valproic Acid might play roles by targeting key DE-ERSGs in OP. The expression validation analysis of key DE-ERSGs revealed that RPN2, ERGIC2, and MYO9A was significantly expressed in the GSE62402. Ultimately, The blood samples RT-qPCR verification results show that RPN2, ERGIC2, and MYO9A were significantly lower in OP samples compared to normal samples (p < 0.05), whereas there was no difference in the expression levels of FOXO3.</p><p><strong>Conclusion: </strong>RPN2, FOXO3, ERGIC2 and MYO9A as the biomarkers associated with ERS in OP by bioinformatics analysis, which may provide new biological targets for clinical treatment.</p>\",\"PeriodicalId\":14131,\"journal\":{\"name\":\"International Journal of General Medicine\",\"volume\":\"17 \",\"pages\":\"5359-5371\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583764/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of General Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/IJGM.S486776\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of General Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJGM.S486776","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
背景：内质网应激（ERS）与骨质疏松症（OP）密切相关：内质网应激（ERS）与骨质疏松症（OP）密切相关。为了探索ERS相关基因在OP中的作用及其分子机制：方法：从基因表达总库（GEO）数据库中检索与 OP 相关的转录组数据。应用加权基因共表达网络分析（WGCNA）筛选 OP 相关基因。通过重叠 OP 相关基因、差异表达基因（DEGs）和 ERS 相关基因，确定 OP 和对照组之间的 ERS 相关差异表达基因（DE-ERSGs）。ERS相关基因。对基因本体（GO）和京都基因组百科全书（KEGG）进行了分析，以探索其功能。受体操作特征曲线（ROC）评估了 DE-ERSGs 的诊断价值，比较毒物基因组学数据库（CTD）用于预测关键 DE-ERSGs 的靶向药物。最后，通过实时定量聚合酶链反应（RT-qPCR）验证了生物标志物的表达：结果：共在 OP 患者中筛选出 10 个 DE-ERSG。GO和KEGG分析表明，它们在酒精性肝病、子宫内膜癌和甘油脂代谢中富集。ROC曲线分析显示，RPN2、FOXO3、ERGIC2和MYO9A具有显著的诊断价值，因此被确定为关键DE-ERSGs。此外，关键DE-ERSGs-药物相互作用网络显示，一些药物如双酚A、顺铂、环孢素和丙戊酸可能通过靶向OP中的关键DE-ERSGs发挥作用。关键 DE-ERSGs 的表达验证分析表明，RPN2、ERGIC2 和 MYO9A 在 GSE62402 中有显著表达。最终，血液样本 RT-qPCR 验证结果显示，与正常样本相比，RPN2、ERGIC2 和 MYO9A 在 OP 样本中的表达量明显降低（P < 0.05），而 FOXO3 的表达量则没有差异：结论：通过生物信息学分析，RPN2、FOXO3、ERGIC2和MYO9A是与OP ERS相关的生物标志物，它们可能为临床治疗提供新的生物学靶点。
Bioinformatics Analysis and Experimental Validation of Endoplasmic Reticulum Stress-Related Genes in Osteoporosis.
Background: Endoplasmic reticulum stress (ERS) is closely associated with Osteoporosis (OP). In order to explore the role of ERS related genes in OP and its molecular mechanism.
Methods: OP-related transcriptome data were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to screen OP-related genes. Differentially expressed ERS-related genes (DE-ERSGs) between OP and controls were identified by overlapping OP-related, differentially expressed genes (DEGs), and ERS-related genes. ERS-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore their functions. Receiver operating characteristic (ROC) curves assessed the diagnostic value of DE-ERSGs, and comparative toxicogenomics database (CTD) was used to predict targeting agents for key DE-ERSGs. Finally, biomarker expression was verified by real time quantitative polymerase chain reaction (RT-qPCR).
Results: A total of 10 DE-ERSGs were screened in OP patients. GO and KEGG analyses indicated their enrichment in Alcoholic liver disease, Endometrial cancer, and Glycerolipid metabolism. ROC curve analysis revealed that RPN2, FOXO3, ERGIC2, and MYO9A had significant diagnostic value, thus being identified as key DE-ERSGs. Moreover, the key DE-ERSGs-drug interaction network showed that some drugs such as bisphenol A, Cisplatin, Cyclosporine, and Valproic Acid might play roles by targeting key DE-ERSGs in OP. The expression validation analysis of key DE-ERSGs revealed that RPN2, ERGIC2, and MYO9A was significantly expressed in the GSE62402. Ultimately, The blood samples RT-qPCR verification results show that RPN2, ERGIC2, and MYO9A were significantly lower in OP samples compared to normal samples (p < 0.05), whereas there was no difference in the expression levels of FOXO3.
Conclusion: RPN2, FOXO3, ERGIC2 and MYO9A as the biomarkers associated with ERS in OP by bioinformatics analysis, which may provide new biological targets for clinical treatment.
期刊介绍：
The International Journal of General Medicine is an international, peer-reviewed, open access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. The journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas.
A key focus of the journal is the elucidation of disease processes and management protocols resulting in improved outcomes for the patient. Patient perspectives such as satisfaction, quality of life, health literacy and communication and their role in developing new healthcare programs and optimizing clinical outcomes are major areas of interest for the journal.
As of 1st April 2019, the International Journal of General Medicine will no longer consider meta-analyses for publication.
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