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image of Integrated Multi-omics Analysis of Hub Genes and miRNA Interactions in Hypertrophic Cardiomyopathy

Abstract

Background

Hypertrophic Cardiomyopathy (HCM) is a complex cardiac disorder marked by the thickening of the heart muscle.

Method

HCM and normal control cell lines were cultured in DMEM with 12.5% FBS and 1% penicillin-streptomycin at 37°C and 5% CO. Differentially expressed genes (DEGs) were identified from GSE32453, GSE53408, and GSE113439 datasets using the limma package in R. Hub genes were determined through protein-protein interaction (PPI) network and Cytoscape analysis and validated Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. Gene enrichment, miRNA predictions, drug prediction, and molecular docking analyses were conducted for functional enrichment and to explore hub gene-associated drugs.

Results

To identify DEGs and hub genes implicated in HCM, we analyzed three Gene Expression Omnibus (GEO) datasets (GSE32453, GSE53404, and GSE1134439), extracting the top 1000 DEGs. Venn analysis revealed 21 common down-regulated genes. PPI analysis identified these six as key hub genes, including Iron Response Element Binding Protein 2 (IREB2), Protein Tyrosine Phosphatase, Non-Receptor Type 11 (PTPN11), IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), Phosphoglucomutase 2 (PGM2), DIS3 RNA Exonuclease 3' to 5' (DIS3), Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1) in HCM patients. Gene enrichment analysis highlighted the involvement of these genes in cellular functions such as energy metabolism and growth factor signaling, suggesting their role in the disease's progression. Validation using an additional dataset (GSE36961) confirmed significant down-regulation of all hub genes in HCM samples, supported by Receiver Operating Characteristic (ROC) curve analysis that demonstrated their diagnostic potential. Furthermore, miRNA analysis identified six up-regulated miRNAs (miR-124, miR-29b, miR-330, miR-34a, miR-375, and miR-451) that likely contribute to the dysregulation of these hub genes. Drug prediction analysis identified various potential therapeutic compounds targeting these hub genes. Molecular docking revealed favorable binding affinities, supporting the therapeutic potential of these drugs in modulating hub gene activity.

Conclusion

Our findings suggest that IREB2, PTPN11, IQGAP1, PGM2, DIS3, and GFPT1 hub genes and their associated regulatory pathways may serve as biomarkers and therapeutic targets for HCM, potentially improving diagnosis and treatment strategies.

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2025-03-26
2025-10-18

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/content/journals/cg/10.2174/0113892029363785250311084956
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Integrated Multi-omics Analysis of Hub Genes and miRNA Interactions in Hypertrophic Cardiomyopathy
Bentham Science Publishers ; https://doi.org/10.2174/0113892029363785250311084956
/content/journals/cg/10.2174/0113892029363785250311084956
/content/journals/cg/10.2174/0113892029363785250311084956
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  • Article Type:     Research Article
Keywords: miRNAs ; treatment ; HCM ; hub genes ; diagnosis

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