{"title":"共享中枢基因介导的cAMP信号通路失调：甲状腺癌和Graves病的诊断、预后和治疗见解","authors":"Tingting Hu, Ruqiong Sun, Juanfei Zhu","doi":"10.2174/0113862073389123250723210633","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Graves' disease and Thyroid cancer share overlapping molecular mechanisms that may reveal potential biomarkers and therapeutic targets. Identifying shared hub genes can provide insights into disease progression and improve diagnosis and treatment strategies.</p><p><strong>Methodology: </strong>Gene expression profiles from Graves' disease (GSE71956) and thyroid cancer (GSE153659) datasets were analyzed to identify differentially expressed genes (DEGs) using the limma package. Common DEGs were identified through cross-dataset comparison, and hub genes were determined based on the degree method. CD44, RHOC, HCN4, and MYH10 hub genes were validated using RT-qPCR in thyroid cancer and normal cell lines and analyzed for functional roles via siRNA-mediated knockdown experiments. miRNA regulators of hub genes were predicted using TargetScan and validated with RT-qPCR. Promoter methylation, mutation, and copy number variation (CNV) analyses were conducted using OncoDB and cBioPortal. Prognostic significance was assessed using the cSurvival and GENT2 databases. Functional enrichment analysis was performed using DAVID, GeneMANIA, and GSCA. miRNA target prediction was carried out with TargetScan, and expression correlation analysis was performed using GEPIA2.</p><p><strong>Results: </strong>Twenty-three common DEGs were identified, with CD44, RHOC, HCN4, and MYH10 emerging as key hub genes. RT-qPCR showed significant (p < 0.001) upregulation of these genes in thyroid cancer cell lines. Functional analysis linked these genes to cAMP signaling and EMT pathways, with promoter hypomethylation, CNV amplifications, and mutations contributing to their dysregulation. CD44 and RHOC knockdown significantly (p < 0.01) reduced proliferation, colony formation, and migration in SW579 cells. Predicted tumor-suppressive miRNAs, including hsa-miR-199a-3p and hsa-miR-455-3p.2, were significantly (p < 0.0001) downregulated in thyroid cancer.</p><p><strong>Conclusion: </strong>CD44, RHOC, HCN4, and MYH10 were identified as shared hub genes between Graves' disease and thyroid cancer, with functional roles in oncogenic pathways. Their diagnostic and therapeutic potential offers novel insights into thyroid disease pathogenesis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dysregulation of the cAMP Signaling Pathway Mediated by Shared Hub Genes: Diagnostic, Prognostic, and Therapeutic Insights into Thyroid Cancer and Graves' Disease.\",\"authors\":\"Tingting Hu, Ruqiong Sun, Juanfei Zhu\",\"doi\":\"10.2174/0113862073389123250723210633\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Graves' disease and Thyroid cancer share overlapping molecular mechanisms that may reveal potential biomarkers and therapeutic targets. Identifying shared hub genes can provide insights into disease progression and improve diagnosis and treatment strategies.</p><p><strong>Methodology: </strong>Gene expression profiles from Graves' disease (GSE71956) and thyroid cancer (GSE153659) datasets were analyzed to identify differentially expressed genes (DEGs) using the limma package. Common DEGs were identified through cross-dataset comparison, and hub genes were determined based on the degree method. CD44, RHOC, HCN4, and MYH10 hub genes were validated using RT-qPCR in thyroid cancer and normal cell lines and analyzed for functional roles via siRNA-mediated knockdown experiments. miRNA regulators of hub genes were predicted using TargetScan and validated with RT-qPCR. Promoter methylation, mutation, and copy number variation (CNV) analyses were conducted using OncoDB and cBioPortal. Prognostic significance was assessed using the cSurvival and GENT2 databases. Functional enrichment analysis was performed using DAVID, GeneMANIA, and GSCA. miRNA target prediction was carried out with TargetScan, and expression correlation analysis was performed using GEPIA2.</p><p><strong>Results: </strong>Twenty-three common DEGs were identified, with CD44, RHOC, HCN4, and MYH10 emerging as key hub genes. RT-qPCR showed significant (p < 0.001) upregulation of these genes in thyroid cancer cell lines. Functional analysis linked these genes to cAMP signaling and EMT pathways, with promoter hypomethylation, CNV amplifications, and mutations contributing to their dysregulation. CD44 and RHOC knockdown significantly (p < 0.01) reduced proliferation, colony formation, and migration in SW579 cells. Predicted tumor-suppressive miRNAs, including hsa-miR-199a-3p and hsa-miR-455-3p.2, were significantly (p < 0.0001) downregulated in thyroid cancer.</p><p><strong>Conclusion: </strong>CD44, RHOC, HCN4, and MYH10 were identified as shared hub genes between Graves' disease and thyroid cancer, with functional roles in oncogenic pathways. Their diagnostic and therapeutic potential offers novel insights into thyroid disease pathogenesis.</p>\",\"PeriodicalId\":10491,\"journal\":{\"name\":\"Combinatorial chemistry & high throughput screening\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Combinatorial chemistry & high throughput screening\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0113862073389123250723210633\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Combinatorial chemistry & high throughput screening","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113862073389123250723210633","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Dysregulation of the cAMP Signaling Pathway Mediated by Shared Hub Genes: Diagnostic, Prognostic, and Therapeutic Insights into Thyroid Cancer and Graves' Disease.
Background: Graves' disease and Thyroid cancer share overlapping molecular mechanisms that may reveal potential biomarkers and therapeutic targets. Identifying shared hub genes can provide insights into disease progression and improve diagnosis and treatment strategies.
Methodology: Gene expression profiles from Graves' disease (GSE71956) and thyroid cancer (GSE153659) datasets were analyzed to identify differentially expressed genes (DEGs) using the limma package. Common DEGs were identified through cross-dataset comparison, and hub genes were determined based on the degree method. CD44, RHOC, HCN4, and MYH10 hub genes were validated using RT-qPCR in thyroid cancer and normal cell lines and analyzed for functional roles via siRNA-mediated knockdown experiments. miRNA regulators of hub genes were predicted using TargetScan and validated with RT-qPCR. Promoter methylation, mutation, and copy number variation (CNV) analyses were conducted using OncoDB and cBioPortal. Prognostic significance was assessed using the cSurvival and GENT2 databases. Functional enrichment analysis was performed using DAVID, GeneMANIA, and GSCA. miRNA target prediction was carried out with TargetScan, and expression correlation analysis was performed using GEPIA2.
Results: Twenty-three common DEGs were identified, with CD44, RHOC, HCN4, and MYH10 emerging as key hub genes. RT-qPCR showed significant (p < 0.001) upregulation of these genes in thyroid cancer cell lines. Functional analysis linked these genes to cAMP signaling and EMT pathways, with promoter hypomethylation, CNV amplifications, and mutations contributing to their dysregulation. CD44 and RHOC knockdown significantly (p < 0.01) reduced proliferation, colony formation, and migration in SW579 cells. Predicted tumor-suppressive miRNAs, including hsa-miR-199a-3p and hsa-miR-455-3p.2, were significantly (p < 0.0001) downregulated in thyroid cancer.
Conclusion: CD44, RHOC, HCN4, and MYH10 were identified as shared hub genes between Graves' disease and thyroid cancer, with functional roles in oncogenic pathways. Their diagnostic and therapeutic potential offers novel insights into thyroid disease pathogenesis.
期刊介绍：
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
Target identification and validation
Assay design, development, miniaturization and comparison
High throughput/high content/in silico screening and associated technologies
Label-free detection technologies and applications
Stem cell technologies
Biomarkers
ADMET/PK/PD methodologies and screening
Probe discovery and development, hit to lead optimization
Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries)
Chemical library design and chemical diversity
Chemo/bio-informatics, data mining
Compound management
Pharmacognosy
Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products)
Natural Product Analytical Studies
Bipharmaceutical studies of Natural products
Drug repurposing
Data management and statistical analysis
Laboratory automation, robotics, microfluidics, signal detection technologies
Current & Future Institutional Research Profile
Technology transfer, legal and licensing issues
Patents.
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