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An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice
Published on: January 12, 2024
Identification of FOXK1 and SEMA7A as key genes associated with m6A-related programmed cell death in diabetic
Jie Yang1, Zhenyu Wu2, Ningning Dong3
1Zhejiang Hospital, Hangzhou, Zhejiang, 310000, China.
Background:
Diabetic retinopathy (DR), a serious microvascular complication of diabetes, has a complex pathogenic mechanism that is intricately linked to programmed cell death (PCD) and also to N6-methyladenosine (m6A) modification. The objective of this research was to pinpoint crucial genes related to m6A-related PCD in DR using transcriptomic data, offering novel targets and a theoretical basis for the pathogenesis of DR.
Methods:
In this study, transcriptomic data of DR samples and control samples were obtained from a public database. Meanwhile, m6A-and PCD-related genes were retrieved from the literature. Candidate genes were identified via differential expression and correlation analyses. Using constructed protein-protein interaction (PPI) networks, a machine learning algorithms screened for feature genes, which underwent expression validation to determine key genes. A predictive nomogram was subsequently developed and its performance evaluated. Enrichment analysis, along with immune infiltration analysis were carried out. Finally, molecular regulatory networks and molecular docking was performed.
Results:
Initially, 3,716 differentially expressed genes between DR and control samples (DRDEGs) were identified. By intersecting DRDEGs with PCD-related genes and m⁶A-related differentially expressed genes, followed by Spearman correlation analysis, 58 candidate genes were identified. Subsequently, Forkhead box K1 (FOXK1) and Semaphorin 7 A (SEMA7A) were identified as key genes through PPI, machine learning, and expression analyses. Furthermore, the two key genes constructed a well accurate nomogram for DR diagnosis. GSEA revealed their critical roles in DR pathogenesis. Moreover, immune infiltration analysis highlighted the involvement of immune dysregulation in DR. The constructed TF-mRNA-miRNA regulatory network contained 2 key genes, 14 transcription factors, and 12 miRNAs (e.g. BRCA1-FOXK1-mmu-miR-7234-3p). Molecular docking showed that decitabine and other drugs bound well to FOXK1,warranting further experimental investigation into their therapeutic efficacy.
Conclusion:
This study identified FOXK1 and SEMA7A as key genes in DR related to m6A-associated programmed cell death, which may provide a new direction for subsequent research on diagnosis and treatment.
Insights
This study identifies FOXK1 and SEMA7A as key genes in diabetic retinopathy (DR) linked to N6-methyladenosine (m⁶A)-associated programmed cell death (PCD). These findings offer new diagnostic and therapeutic targets for DR.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a severe complication of diabetes, involving complex mechanisms of programmed cell death (PCD) and N6-methyladenosine (m⁶A) modification.
- Understanding these molecular pathways is crucial for developing effective treatments for DR.
Purpose of the Study:
- To identify key genes associated with m⁶A-related PCD in DR using transcriptomic data.
- To provide novel molecular targets and a theoretical basis for DR pathogenesis.
Main Methods:
- Transcriptomic data analysis of DR and control samples.
- Identification of differentially expressed genes (DEGs) and correlation with m⁶A and PCD-related genes.
- Protein-protein interaction (PPI) networks, machine learning, and expression validation to pinpoint key genes (FOXK1 and SEMA7A).
- Development of a predictive nomogram, enrichment analysis, immune infiltration analysis, and molecular docking.
Main Results:
- 3,716 DEGs were identified between DR and control samples.
- Forkhead box K1 (FOXK1) and Semaphorin 7A (SEMA7A) were identified as key genes.
- A predictive nomogram using FOXK1 and SEMA7A demonstrated high accuracy for DR diagnosis.
- Immune dysregulation and specific regulatory networks (e.g., BRCA1-FOXK1-mmu-miR-7234-3p) were implicated in DR.
- Molecular docking suggested potential therapeutic efficacy for drugs like decitabine targeting FOXK1.
Conclusions:
- FOXK1 and SEMA7A are identified as critical genes in m⁶A-associated PCD in DR.
- These genes offer promising new directions for DR diagnosis and treatment strategies.
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