Related Experiment Video
Updated: Sep 11, 2025
Author Spotlight: Integrated Multi-Omics Analysis for Unveiling Multicellular Immune Signatures in Clinical Heart Attack Cohorts
Published on: September 20, 2024
Multi-omics approach reveals CCND1, GABPA, HIF1A, and SOX6 as key regulators and prognostic markers in heart failure
Ping He1,2, Lang Deng3,4, Kaijie Wu5
1Fifth School of Clinical Medicine of Zhejiang, Huzhou Central Hospital, Chinese Medical University, Huzhou, 313000, Zhejiang, China.
Insights
This study identifies key genes like CCND1 and HIF1A as potential biomarkers for heart failure (HF). Findings offer insights into HF progression and therapeutic targets for better disease management.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Genomics
Background:
- Heart failure (HF) is a complex, progressive condition with incompletely understood molecular underpinnings.
- Identifying novel biomarkers and therapeutic targets is crucial for effective HF management.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in heart failure (HF) patients.
- To explore the roles of key genes (hub genes) in HF pathophysiology.
- To develop a predictive risk model for HF disease progression and identify potential therapeutic targets.
Main Methods:
- Analysis of gene expression datasets from human HF and normal cardiomyocyte cell lines.
- Construction of Protein-Protein Interaction (PPI) networks and analysis of immune cell infiltration.
- Development of a risk prediction model using LASSO regression and drug screening via CMap.
Main Results:
- Identified 182 common DEGs in HF, with CCND1, GABPA, HIF1A, and SOX6 as significant hub genes.
- Established a risk model correlated with HF progression and observed altered immune cell profiles.
- Overexpression of CCND1 and HIF1A impaired cell proliferation and migration, confirming their role in HF.
Conclusions:
- CCND1, GABPA, HIF1A, and SOX6 are potential biomarkers for heart failure (HF).
- Findings illuminate the roles of immune infiltration and miRNA regulation in HF.
- The study provides insights into novel therapeutic targets for HF management and highlights gene regulation's importance in disease progression.
Introduction:
Heart failure (HF) is a progressive condition with complex molecular mechanisms. This study aims to identify potential biomarkers and therapeutic targets by analyzing differentially expressed genes (DEGs) in HF patients, exploring the roles of hub genes, and developing a risk model for predicting disease progression.
Methodology:
We cultured five human HF cell lines and five normal coronary cardiomyocyte cell lines. Gene expression datasets were retrieved from the Gene Expression Omnibus (GEO) database and analyzed using limma. Protein-Protein Interaction (PPI) networks were constructed with STRING, and immune cell infiltration was analyzed using CIBERSORT. A risk model was built using LASSO regression. Drug screening was performed via CMap, and overexpression studies of CCND1 and HIF1A were conducted in AC16 and SEKHEP1 cells via cell proliferation, colony formation, and wound healing assays.
Results:
We identified 182 common DEGs associated with HF. Hub genes CCND1, GABPA, HIF1A, and SOX6 were central in the PPI network. LASSO regression established a risk model linked to disease progression. Immune infiltration analysis revealed altered immune cell profiles in HF. The miRNA-mRNA network showed interactions of hsa-miR-93-5p, hsa-miR-802, hsa-miR-199a-5p, and hsa-miR-203a-3p with hub genes. Overexpression of CCND1 and HIF1A in cell lines impaired proliferation, colony formation, and migration, implicating their role in HF pathophysiology.
Conclusion:
CCND1, GABPA, HIF1A, and SOX6 may serve as biomarkers for HF. Our findings provide valuable insights into immune infiltration, miRNA regulation, and the identification of therapeutic targets for HF management. These results highlight the role of gene regulation in HF progression and may guide future therapeutic interventions.
Related Concept Videos
01:29Heart Failure II: Pathophysiology
01:17Pathophysiology of Heart Failure
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
02:23Master Transcription Regulators