Combined microRNA and mRNA expression analysis in pediatric multiple sclerosis: an integrated approach to uncover novel pathogenic mechanisms of the disease.
Open accessAbstract
Multiple sclerosis (MS) is a complex disease of the CNS that usually affects young adults, although 3-5% of cases are diagnosed in childhood and adolescence (hence called pediatric MS, PedMS). Genetic predisposition, among other factors, seems to contribute to the risk of the onset, in pediatric as in adult ages, but few studies have investigated the genetic 'environmentally naïve' load of PedMS. The main goal of this study was to identify circulating markers (miRNAs), target genes (mRNAs) and functional pathways associated with PedMS; we also verified the impact of miRNAs on clinical features, i.e. disability and cognitive performances. The investigation was performed in 19 PedMS and 20 pediatric controls (PCs) using a High-Throughput Next-generation Sequencing (HT-NGS) approach followed by an integrated bioinformatics/biostatistics analysis. Twelve miRNAs were significantly upregulated (let-7a-5p, let-7b-5p, miR-25-3p, miR-125a-5p, miR-942-5p, miR-221-3p, miR-652-3p, miR-182-5p, miR-185-5p, miR-181a-5p, miR-320a, miR-99b-5p) and 1 miRNA was downregulated (miR-148b-3p) in PedMS compared with PCs. The interactions between the significant miRNAs and their targets uncovered predicted genes (i.e. TNFSF13B, TLR2, BACH2, KLF4) related to immunological functions, as well as genes involved in autophagy-related processes (i.e. ATG16L1, SORT1, LAMP2) and ATPase activity (i.e. ABCA1, GPX3). No significant molecular profiles were associated with any PedMS demographic/clinical features. Both miRNAs and mRNA expressions predicted the phenotypes (PedMS-PC) with an accuracy of 92% and 91%, respectively. In our view, this original strategy of contemporary miRNA/mRNA analysis may help to shed light in the genetic background of the disease, suggesting further molecular investigations in novel pathogenic mechanisms.
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Combining microRNA and mRNA expression analysis in pediatric multiple sclerosis is an integrated approach to uncovering novel disease pathogenic mechanisms.
“Liguori discovered that combining microRNA and mRNA expression analysis in pediatric multiple sclerosis is an integrated approach to uncovering novel disease pathogenic mechanisms [12].”
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- Authors
- Liguori, M., Nuzziello, N., Licciulli, F., Consiglio, A., Simone, M., Viterbo, R. G., Creanza, T. M., Ancona, N., Tortorella, C., Margari, L., Grillo, G., Giordano, P., Liuni, S., & Trojano, M.
- Affiliations
- Institute of Biomedical Technologies (IT)
- University of Bari Aldo Moro (IT)
- Institute of Intelligent Systems for Automation (IT)
- Azienda Ospedaliera San Camillo-Forlanini (IT)
- Ospedale Pediatrico Giovanni XXIII (IT)
- Department of Basic Sciences, Neurosciences and Sense Organs, University of Bari, 70125 Bari, Italy
- Corresponding author
- Liguori, Maria
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-10-26
- Volume
- 27
- Issue
- 1
- Pages
- 66-79
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2766213087
- Cited by
- 83
- References
- 64
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 10 · 2022: 15 · 2021: 9 · 2020: 17 · 2019: 11 · 2018: 8
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by-nc-nd)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- Fondazione Italiana Sclerosi Multipla
- FISM (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
- pediatric multiple sclerosis, microRNA expression, mRNA expression, circulating biomarkers, miRNA target genes, autophagy, TNFSF13B, TLR2, BACH2, KLF4, ATG16L1, SORT1, LAMP2, ABCA1, glutathione peroxidase 3, disability, cognitive performance, pathogenesis
- MeSH terms
- Kruppel-Like Factor 4, Adolescent, Child, Child, Preschool, Female, Gene Expression Regulation, Humans, Male, Multiple Sclerosis, RNA, Messenger, Biomarkers, Sequence Analysis, RNA, Computational Biology, Genetic Predisposition to Disease, MicroRNAs, Transcriptome
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