Investigating the Role of MicroRNA and Transcription Factor Co-regulatory Networks in Multiple Sclerosis Pathogenesis.
Open accessAbstract
MicroRNAs (miRNAs) and transcription factors (TFs) play key roles in complex multifactorial diseases like multiple sclerosis (MS). Starting from the miRNomic profile previously associated with a cohort of pediatric MS (PedMS) patients, we applied a combined molecular and computational approach in order to verify published data in patients with adult-onset MS (AOMS). Six out of the 13 selected miRNAs (miR-320a, miR-125a-5p, miR-652-3p, miR-185-5p, miR-942-5p, miR-25-3p) were significantly upregulated in PedMS and AOMS patients, suggesting that they may be considered circulating biomarkers distinctive of the disease independently from age. A computational and unbiased miRNA-based screening of target genes not necessarily associated to MS was then performed in order to provide an extensive view of the genetic mechanisms underlying the disease. A comprehensive MS-specific miRNA-TF co-regulatory network was hypothesized; among others, SP1, RELA, NF-κB, TP53, AR, MYC, HDAC1, and STAT3 regulated the transcription of 61 targets. Interestingly, NF-κB and STAT3 cooperatively regulate the expression of immune response genes and control the cross-talk between inflammatory and immune cells. Further functional analysis will be performed on the identified critical hubs. Above all, in our view, this approach supports the need of multidisciplinary strategies for shedding light into the pathogenesis of MS.
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Many studies have shown a close relationship between microRNAs and mRNAs in disease regulation, particularly the negative feedback regulation of targeted mRNAs by their miRNAs.
“Many other studies have shown a close relationship between microRNAs and mRNAs in disease regulation, particularly the negative feedback regulation of targeted mRNAs by their miRNAs [13–14]”
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- Authors
- Nuzziello, N., Vilardo, L., Pelucchi, P., Consiglio, A., Liuni, S., Trojano, M., & Liguori, M.
- Affiliations
- Institute of Biomedical Technologies (IT)
- Department of Basic Sciences, Neurosciences and Sense Organs, University of Bari, 70124 Bari, Italy
- Corresponding author
- Liguori, Maria
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2018-11-20
- Volume
- 19
- Issue
- 11
- Pages
- 3652
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC6274935
- OpenAlex
- W2901580939
- Cited by
- 46
- References
- 68
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 9 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 6
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by)
- Funders
- Fondazione Italiana Sclerosi Multipla (2014/R/10)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- multiple sclerosis, microRNA, transcription factors, pediatric multiple sclerosis, adult-onset multiple sclerosis, circulating biomarkers, miRNA target genes, NF-κB, STAT3, Sp1, RelA, TP53, c-Myc, HDAC1, immune response genes, pathogenesis
- MeSH terms
- Adult, Base Sequence, Female, Humans, Luciferases, Male, Multiple Sclerosis, ROC Curve, Transcription Factors, Reproducibility of Results, Gene Expression Regulation, Neoplastic, Age of Onset, Genes, Reporter, Gene Expression Profiling, MicroRNAs, Gene Regulatory Networks, HEK293 Cells
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