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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Network Pharmacology Approaches Used to Identify Therapeutic Molecules for Chronic Venous Disease Based on Potential
Oscar Salvador Barrera-Vázquez1, Juan Luis Escobar-Ramírez1, Gil Alfonso Magos-Guerrero1
1Department of Pharmacology, Faculty of Medicine, University National Autonomous of Mexico (UNAM), Mexico City 04510, Mexico.
Abstract:
Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to identify, by network analysis, the miRNAs involved in CVD as potential biomarkers, either by interacting with small molecules such as toxins and pollutants or by searching for new drugs. Our study shows an updated landscape of the signaling pathways involving miRNAs in CVD pathology. This latest research includes data found through experimental tests and uses predictions to propose both miRNAs and genes as potential biomarkers to develop diagnostic and therapeutic methods for the early detection of CVD in the clinical setting. In addition, our pharmacological network analysis has, for the first time, shown how to use these potential biomarkers to find small molecules that may regulate them. Between the small molecules in this research, toxins, pollutants, and drugs showed outstanding interactions with these miRNAs. One of them, hesperidin, a widely prescribed drug for treating CVD and modulating the gene expression associated with CVD, was used as a reference for searching for new molecules that may interact with miRNAs involved in CVD. Among the drugs that exhibit the same miRNA expression profile as hesperidin, potential candidates include desoximetasone, curcumin, flurandrenolide, trifluridine, fludrocortisone, diflorasone, gemcitabine, floxuridine, and reversine. Further investigation of these drugs is essential to improve the treatment of cardiovascular disease. Additionally, supporting the clinical use of miRNAs as biomarkers for diagnosing and predicting CVD is crucial.
Insights
MicroRNAs (miRNAs) are key biomarkers for chronic venous disease (CVD) diagnosis and treatment. This study identifies novel miRNA-based diagnostic and therapeutic strategies for CVD, including drug discovery.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Genomics
Background:
- Chronic venous disease (CVD) is a widespread condition, particularly in the elderly, with higher prevalence in women.
- MicroRNAs (miRNAs) play a role in cardiovascular disease (CVD) development by modulating gene expression.
- Seven genes (CDS2, HDAC5, PPP6R2, PRBC2B, TBC1D22A, WNK1, PABPC3) have been identified as miRNA targets in CVD.
Purpose of the Study:
- To identify microRNAs (miRNAs) involved in chronic venous disease (CVD) through network analysis for potential biomarker development.
- To explore interactions between miRNAs, small molecules (toxins, pollutants), and drugs for novel diagnostic and therapeutic strategies in CVD.
- To update the understanding of signaling pathways involving miRNAs in CVD pathology.
Main Methods:
- Network analysis to identify miRNAs associated with CVD.
- Experimental data and predictive methods to identify potential miRNA and gene biomarkers.
- Pharmacological network analysis to discover small molecules regulating identified miRNAs.
Main Results:
- An updated landscape of miRNA-involved signaling pathways in CVD pathology was revealed.
- Toxins, pollutants, and drugs demonstrated significant interactions with CVD-related miRNAs.
- Hesperidin, a CVD drug, was used as a reference to identify potential new therapeutic molecules like desoximetasone, curcumin, and gemcitabine.
Conclusions:
- MicroRNAs (miRNAs) are crucial for CVD diagnosis and treatment, offering novel molecular insights.
- The study proposes miRNAs and specific genes as potential biomarkers for early CVD detection and management.
- Pharmacological analysis identified potential new drug candidates that modulate miRNAs involved in CVD, supporting clinical applications.

