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CASP1 as a key autophagy-related gene in atherosclerosis: Identification by bioinformatics analysis and experimental
Han Gao1, Yuanling Guo1, Lang Wang1
1Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Objective:
This study identified potential autophagy-related genes (ARGs) in atherosclerosis using bioinformatics strategies, aiming to explore novel therapeutic targets for the clinical management of atherosclerosis.
Methods:
Four gene expression datasets associated with atherosclerosis (GSE100927, GSE43292, GSE28829, and GSE20129) were retrieved from the GEO database of the NCBI and subjected to comprehensive analysis. A list of ARGs was compiled by accessing the HADb. AR-DEGs were screened using the "limma" package in R software. Thereafter, six core genes were identified through the combined application of three machine learning algorithms and PPI network analysis, with subsequent validation conducted using external datasets GSE28829 and GSE20129. Additional analyses included GO annotation, KEGG pathway enrichment, drug prediction, immune infiltration assessment, ceRNA network establishment, and transcription factor (TF) regulatory network analysis. Finally, the expression levels of CASP1 in both in vivo and in vitro models were quantified using WB, RT-qPCR, and IF assays.
Results:
A total of 13 AR-DEGs were detected with significant expression differences between the AS group and the control group. After integrative screening via PPI network analysis and machine learning algorithms, followed by validation against external datasets GSE28829 and GSE20129, PRKCD, SERPINA1, CASP1, CXCR4, and CCR2 were confirmed as characteristic biomarkers for AS, and their corresponding microRNAs (miRNAs) were predicted. Immune infiltration analysis indicated that these characteristic genes were correlated with immune cells. Moreover, in vivo and in vitro experimental results demonstrated that CASP1 was highly expressed in AS samples.
Conclusion:
PRKCD, SERPINA1, CASP1, CXCR4, and CCR2 were identified as key genes in atherosclerosis, and their associated ceRNA and TF regulatory networks were predicted. Among these key genes, CASP1 is a promising candidate associated with atherosclerosis and worthy of further study.
Insights
This study identified five key autophagy-related genes (ARGs) in atherosclerosis, including CASP1, as potential therapeutic targets. These genes are linked to immune cell infiltration and offer new avenues for treating atherosclerosis.
Area of Science:
- Cardiovascular Research
- Genetics and Genomics
- Molecular Biology
Background:
- Atherosclerosis is a complex cardiovascular disease with limited therapeutic targets.
- Autophagy-related genes (ARGs) play a role in cellular processes relevant to atherosclerosis.
- Identifying novel ARGs can lead to new treatment strategies.
Purpose of the Study:
- To identify potential autophagy-related genes (ARGs) associated with atherosclerosis.
- To explore novel therapeutic targets for atherosclerosis using bioinformatics.
- To investigate the role of ARGs in atherosclerosis pathogenesis.
Main Methods:
- Utilized four atherosclerosis gene expression datasets from the NCBI GEO database.
- Screened autophagy-related differentially expressed genes (AR-DEGs) using R software.
- Identified core genes via machine learning, PPI network analysis, and external dataset validation.
Main Results:
- Identified 13 AR-DEGs, confirming PRKCD, SERPINA1, CASP1, CXCR4, and CCR2 as characteristic biomarkers for atherosclerosis.
- Predicted corresponding microRNAs (miRNAs) and established ceRNA and transcription factor (TF) regulatory networks.
- Confirmed high CASP1 expression in atherosclerosis models and its correlation with immune cell infiltration.
Conclusions:
- PRKCD, SERPINA1, CASP1, CXCR4, and CCR2 are key genes in atherosclerosis.
- CASP1 is a promising therapeutic target for atherosclerosis.
- The identified regulatory networks provide insights into atherosclerosis mechanisms.
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