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Published on: November 8, 2011
Integrational analysis of miRNAs data sets as a plausible missing linker between Epstein-Barr virus and vitamin D in
Majid Teymoori-Rad1, Sayed-Hamidreza Mozhgani2, Mohadeseh Zarei-Ghobadi3
1Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Given the multifactorial state of autoimmune complex diseases such as multiple sclerosis (MS), it is not clear if different risk factors act jointly or independently. Despite intensive studies investigating multi aspects of MS risk factors, findings with regards to potential biomarkers that may link these risk factors remained largely inconclusive. System biology or data integration utilizes different validated datasets to extract meaningful information and map the plausible biological pathways and networks. As such, we integrated eight transcriptome datasets to find the differentially expressed miRNAs in peripheral blood (PB) between relapsing remitting MS patients (RRMS) and normal group. After identification the targeted genes of miRNAs, the hub genes were used to construct the underlying protein-protein interaction network and signaling pathways. As results, 9 miRNAs were best exemplified by significant dysregulation including hsa-mir-15a, hsa-mir-484, hsa-mir-30d, hsa-mir-145, hsa-mir-363, has-let-7e, hsa-mir-30a, hsa-let-7b, and hsa-mir-146a. System biology analysis of miRNAs in PB of RRMS patients clearly indicates the involvement of miRNAs in many vital pathways and highlighted the possibility of an association between miRNAs with EBV and vitamin D in MS pathogenesis. Described novel pathways and genes related to miRNAs such as Transient receptor potential channels and Acid sphingomyelinase may provide a potential target for therapeutic approaches although further functional studies are warranted to test these candidates.
Insights
This study integrated multiple datasets to identify key microRNAs (miRNAs) in multiple sclerosis (MS) patients. These findings suggest potential links between miRNAs, Epstein-Barr virus (EBV), and vitamin D in MS development.
Area of Science:
- Genomics and Bioinformatics
- Immunology
- Systems Biology
Background:
- Multiple sclerosis (MS) is a complex autoimmune disease with multifactorial origins, where the interplay of risk factors remains unclear.
- Previous research on MS risk factors and potential biomarkers has yielded inconclusive results.
- Systems biology approaches integrating diverse datasets are crucial for understanding complex disease mechanisms.
Purpose of the Study:
- To identify differentially expressed microRNAs (miRNAs) in the peripheral blood of relapsing-remitting MS (RRMS) patients compared to healthy controls.
- To construct protein-protein interaction networks and signaling pathways based on identified miRNA targets.
- To explore potential associations between miRNAs, Epstein-Barr virus (EBV), and vitamin D in MS pathogenesis.
Main Methods:
- Integration of eight transcriptome datasets.
- Differential expression analysis of miRNAs in peripheral blood of RRMS patients.
- Target gene identification for dysregulated miRNAs.
- Construction of protein-protein interaction networks and pathway analysis.
Main Results:
- Nine miRNAs, including hsa-mir-15a, hsa-mir-484, hsa-mir-30d, hsa-mir-145, hsa-mir-363, has-let-7e, hsa-mir-30a, hsa-let-7b, and hsa-mir-146a, showed significant dysregulation.
- Systems biology analysis revealed the involvement of these miRNAs in vital biological pathways.
- Potential associations between miRNAs, EBV, and vitamin D in MS pathogenesis were highlighted.
Conclusions:
- Dysregulated miRNAs in the peripheral blood of RRMS patients play a significant role in disease pathways.
- The study suggests a possible link between miRNAs, EBV, and vitamin D in the development of MS.
- Novel pathways and genes, such as Transient Receptor Potential channels and Acid Sphingomyelinase, may represent potential therapeutic targets for MS.
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