Introduction
Definition of Omics and Its Role in Genomics Research
Omics refers to comprehensive studies of molecules such as genes, proteins, and metabolites, providing insights into biological systems. By leveraging genomics, transcriptomics, and epigenomics, researchers can decode gene regulatory mechanisms, disease pathways, and therapeutic targets.
Overview of Chronic Venous Insufficiency (CVI)
CVI is a vascular condition affecting lower extremity veins, leading to varicose veins, ulcers, and prolonged venous hypertension. Research shows genetic predisposition and epigenetic modifications significantly influence its progression.
Significance of Genetic and Epigenetic Investigations in CVI
Studies integrating omics approaches have identified genetic markers associated with venous dysfunction. Key findings indicate that mRNA-miRNA interactions play a pivotal role in gene regulation within vascular tissues.
Understanding Omics in CVI Research
Genomics, Transcriptomics, and Epigenomics in Vascular Diseases
Omics technologies have revealed multiple genes linked to CVI. Genomics studies explore DNA sequences and mutations, transcriptomics analyzes gene expression patterns, and epigenomics focuses on regulatory mechanisms affecting vascular integrity.
Key Genetic Markers Identified via Omics-Based Approaches
Through multi-omics data integration, researchers have pinpointed genes involved in venous remodeling and inflammation, including:
- VEGFA – regulates angiogenesis and vascular repair.
- CASZ1 – implicated in blood pressure regulation.
- PIEZO1 – mechanotransduction protein affecting venous function.
Role of miRNAs in Gene Expression Modulation
MicroRNAs (miRNAs) function as key post-transcriptional regulators by binding to specific mRNA sequences, altering gene expression. Studies have identified several miRNAs impacting CVI-related genes, further reinforcing mRNA-miRNA interactions as critical modulators of venous health.
Methodology: Omics Data Integration for CVI Studies
Researchers utilized in silico tools to analyze genomic variants influencing CVI.
Steps Involved:
- Data Collection: Genetic and transcriptomic datasets from CVI patient samples were examined.
- miRNA Binding Site Analysis: Tools like MBS, miRBase, and miRWALK were employed to predict mRNA-miRNA binding interactions.
- eQTL Screening: The GTEx portal helped assess expression quantitative trait loci (eQTLs) within vascular tissues.
- Variant Filtering: SNVs affecting miRNA-mediated gene regulation were selected for further analysis.
Omics: Key Findings from Methodological Approach
A combination of computational and literature-based approaches provided insights into potential biomarkers and therapeutic targets in CVI.
Table 1: CVI-Associated SNVs Impacting mRNA-miRNA Interactions
| Gene | Variant ID | Location | miRNA Impact |
|---|---|---|---|
| VEGFA | rs2010963 | 5′-UTR | miR-210-5p affects angiogenesis |
| CASZ1 | rs284299 | Exon | miR-136-5p regulates vascular development |
| PIEZO1 | rs4782432 | Exon | miR-183-5p contributes to venous remodeling |
| ABCA1 | rs2066714 | Exon | miR-17-5p influences lipid metabolism |
| APOE | rs7412 | CDS | miR-4755-3p alters lipid transport |
These findings suggest genetic regulation through miRNA binding plays a vital role in CVI development.
How mRNA-miRNA Interactions Influence CVI
Binding Sites and Genetic Determinants
Identified SNVs impacted miRNA binding efficiency, altering gene expression:
- VEGFA – miRNA binding regulates endothelial repair processes.
- CASZ1 – genetic variations disrupt vascular signaling mechanisms.
- PIEZO1 – mechanosensitive ion channels influenced venous remodeling.
Biological Impact on CVI Progression
Studies suggest that miRNA-mRNA interactions contribute to vascular remodeling, inflammation, and endothelial dysfunction in CVI.
Omics: Results and Key Findings
Omics: Identified SNVs and Their Functional Relevance
Researchers mapped SNVs to miRNA binding regions, revealing:
- Genetic polymorphisms altering miRNA-mediated gene suppression or activation.
- Common miRNAs targeting key vascular genes.
- Pathway disruptions leading to venous insufficiency progression.
Conclusion and Future Perspectives
Omics-driven approaches offer valuable insights into gene regulation, disease mechanisms, and potential therapeutic targets. These findings pave the way for personalized medicine in CVI treatment.
Future studies should emphasize experimental validation and explore miRNA-targeted therapies to improve vascular health.
3. Methodology: Omics Data Integration for CVI Studies
Collection of CVI-Related Genomic and Transcriptomic Datasets
The study utilized published data on genes, single nucleotide variants (SNVs), and miRNAs associated with chronic venous insufficiency (CVI). A comprehensive literature review was conducted using PubMed, screening keywords such as “Chronic Venous Insufficiency GWAS” and “Varicose Veins miRNA.” Articles focusing on venous ulcers or non-genetic risk factors were excluded, resulting in 327 unique SNVs and 75 miRNAs relevant to CVI pathology.
Utilization of In Silico Tools for Predicting mRNA-miRNA Interactions
To investigate regulatory effects, multiple bioinformatics platforms were employed:
- MBS Database (miRNA Binding Site) identified SNVs within miRNA binding regions.
- miRWALK Tool confirmed predicted interactions, cross-referencing known miRNA targets.
- GTEx eQTL Calculator determined expression quantitative trait loci (eQTLs) affecting vascular tissues.
- Genome browsers (UCSC, Ensembl, Franklin) provided genomic mapping and allele frequency data.
Overview of Databases for miRNA Target Prediction
The study used robust databases such as:
- MBS (Genome browsers + TargetScan, PITA, Miranda algorithms)
- miRBase (miRNA sequence and annotation reference)
- miRWALK (Random-forest-based prediction of binding sites)
- GTEx portal (Expression profiling across tissues)
Filtering of Single Nucleotide Variants (SNVs) Affecting Gene Expression
From 326 CVI-associated SNVs, variants were filtered based on:
- Minor Allele Frequency (MAF ≥ 0.05) to prioritize common genetic variations.
- Statistical significance in vascular tissues to identify key regulators.
- Co-localization within miRNA binding regions using positional search tools.
Statistical Significance Testing of eQTLs in Vascular Tissues
Each filtered SNV was tested for its eQTL impact in six target tissues using the GTEx portal:
- Aorta
- Coronary artery
- Tibial artery
- Cultured fibroblast cells
- Skeletal muscle
- Whole blood
Table 1: CVI-Associated SNVs in miRNA Binding Regions
| Gene | Variant ID | Location | MAF | Tissue Impact | miRNA Interaction |
|---|---|---|---|---|---|
| VEGFA | rs2010963 | 5′-UTR | 0.45 | Aorta | miR-210-5p |
| CASZ1 | rs284299 | Exon | 0.49 | Whole blood | miR-136-5p |
| PIEZO1 | rs4782432 | Exon | 0.18 | Multiple arteries | miR-183-5p |
| ABCA1 | rs2066714 | Exon | 0.49 | Coronary artery | miR-17-5p |
| APOE | rs7412 | CDS | 0.17 | Whole blood | miR-4755-3p |
The statistical filtering narrowed down key genetic variants that significantly influence vascular gene expression.
4. Omics: How mRNA-miRNA Interactions Influence CVI
Omics: Explanation of Binding Sites Within Gene Transcripts
MiRNAs regulate gene expression by binding to specific sequences in mRNA, located within:
- 5′-UTR regions—affecting initiation of translation.
- 3′-UTR regions—altering transcript stability.
- Coding sequences (CDS)—modulating protein production.
Genetic Determinants Affecting miRNA-Mediated Regulation
The study identified SNVs in mRNA-miRNA interaction regions that altered regulatory efficiency. Some miRNAs had multiple binding sites, increasing their gene suppression effects.
Impact of Identified SNVs on Vascular Gene Expression
- VEGFA (rs2010963): Regulates angiogenesis, affected by miR-210-5p binding.
- CASZ1 (rs284299): Influences vascular remodeling, modulated by miR-136-5p.
- PIEZO1 (rs4782432): Mechanosensitive ion channels modified by miR-183-5p.
These interactions play a crucial role in venous remodeling and inflammation in CVI.
Table 2: miRNAs Affecting CVI-Associated Genes
| miRNA | Target Gene | Binding Site | Effect on Gene Expression |
|---|---|---|---|
| miR-210-5p | VEGFA | 5′-UTR | Upregulated angiogenesis |
| miR-136-5p | CASZ1 | Exon | Altered vascular remodeling |
| miR-17-5p | ABCA1 | Exon | Lipid metabolism regulation |
| miR-183-5p | PIEZO1 | Exon | Venous remodeling impact |
| miR-4755-3p | APOE | CDS | Affects lipid transport |
How Regulatory Networks Contribute to CVI Pathogenesis
- Genetic mutations modify miRNA binding efficiency, disrupting normal gene function.
- SNVs in vascular mechanotransduction genes such as PIEZO1 contribute to CVI progression.
- Altered miRNA interactions can lead to venous wall instability and inflammation.
5. Omics: Results and Key Findings
Omics: Identified SNVs Influencing miRNA Binding in CVI-Associated Genes
Through extensive bioinformatic analysis, the study identified single nucleotide variants (SNVs) in miRNA binding regions within genes linked to chronic venous insufficiency (CVI). These SNVs are significant as they impact gene expression and regulatory mechanisms, contributing to vascular dysfunction.
The study examined 327 SNVs associated with CVI, filtering them using minor allele frequency (MAF ≥ 0.05) thresholds to prioritize common variants with potential biological impact. Following strict selection criteria, 66 SNVs were found to have expression quantitative trait loci (eQTL) effects, influencing vascular gene activity. These SNVs co-localized with miRNA binding sites, suggesting their direct role in mRNA-miRNA regulatory networks.
Specific Genes Involved: VEGFA, CASZ1, PIEZO1, ABCA1, and APOE
The study focused on five key genes known to regulate vascular remodeling and endothelial function:
- VEGFA – A critical factor in angiogenesis, influencing blood vessel formation.
- CASZ1 – Involved in blood pressure regulation and venous wall integrity.
- PIEZO1 – A mechanotransduction protein impacting venous stiffness.
- ABCA1 – Regulates lipid transport, influencing vascular inflammation.
- APOE – Alters cholesterol metabolism, affecting vascular health.
Each of these genes harbors SNVs affecting miRNA binding efficiency, altering expression profiles.
Common miRNAs Regulating Vascular Dysfunction in CVI Patients
Seven miRNAs were found to influence CVI pathology by interacting with key SNVs. These include:
- miR-210-5p (targets VEGFA) – Regulates angiogenesis and endothelial repair.
- miR-136-5p (targets CASZ1) – Modulates vascular smooth muscle function.
- miR-183-5p (targets PIEZO1) – Affects venous stiffness and remodeling.
- miR-17-5p (targets ABCA1) – Alters lipid metabolism and endothelial inflammation.
- miR-4755-3p (targets APOE) – Impacts cholesterol transport and vascular integrity.
These miRNAs were identified using MBS and miRWALK databases, validating their regulatory effects.
Table 1: CVI-Associated SNVs and Their Functional Relevance
| Gene | Variant ID | Location | miRNA Impact |
|---|---|---|---|
| VEGFA | rs2010963 | 5′-UTR | miR-210-5p affects angiogenesis |
| CASZ1 | rs284299 | Exon | miR-136-5p regulates vascular development |
| PIEZO1 | rs4782432 | Exon | miR-183-5p contributes to venous remodeling |
| ABCA1 | rs2066714 | Exon | miR-17-5p influences lipid metabolism |
| APOE | rs7412 | CDS | miR-4755-3p alters lipid transport |
This table highlights key genetic variants influencing mRNA-miRNA interactions, providing insights into CVI pathogenesis.
Implications for Potential Biomarkers and Therapeutic Strategies
The findings suggest that mRNA-miRNA binding sites could serve as valuable biomarkers for predicting CVI progression.
- Genetic screening for high-risk SNVs may help in early diagnosis.
- miRNA-based therapies targeting dysregulated gene expression could be explored.
- The study lays the groundwork for developing personalized medicine approaches in vascular disease treatment.
6. Conclusion and Future Perspectives
Importance of Omics-Driven Approaches in CVI Research
This study underscores the power of omics integration in unraveling complex gene interactions. By analyzing SNVs in mRNA-miRNA binding regions, researchers can better understand vascular remodeling and endothelial dysfunction in CVI patients.
Potential Applications in Personalized Medicine for Vascular Diseases
Findings from this study open new avenues for precision medicine. Future efforts could:
- Develop gene-targeted therapies for CVI patients.
- Utilize miRNA screening for early disease detection.
- Investigate therapeutic interventions based on individual genetic profiles.
Next Steps in Experimental Validation and Clinical Integration
While bioinformatics tools provide strong predictive insights, further experimental validation is needed to confirm SNV-miRNA interactions.
- Wet lab studies should validate miRNA effects on gene expression.
- Clinical trials could explore miRNA-based treatments for CVI.
- Machine learning models might refine miRNA regulatory predictions.
Encouragement for Further Research into miRNA-Targeted Therapies
This study demonstrates that miRNA binding sites hold significant promise for CVI treatment strategies.
- Researchers should investigate miRNA inhibitors for therapeutic use.
- Identifying additional CVI-associated SNVs could enhance genetic screening programs.
- Collaboration across genomics, bioinformatics, and clinical medicine is key to advancing CVI treatment.
Reference
Sarı-Tunel, F.; Demirkan, A.; Vural, B.; Yıldız, C.E.; Komurcu-Bayrak, E. Omics Data Integration Uncovers mRNA-miRNA Interaction Regions in Genes Associated with Chronic Venous Insufficiency. Genes 2025, 16, 40. https://doi.org/10.3390/genes16010040.
License
This article is distributed under the Creative Commons Attribution (CC BY) 4.0 License. This means it can be freely shared, adapted, and used, as long as appropriate credit is given to the original authors. License details: https://creativecommons.org/licenses/by/4.0/