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Updated: Feb 2, 2026
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Investigating the Role of MicroRNA and Transcription Factor Co-regulatory Networks in Multiple Sclerosis Pathogenesis
Nicoletta Nuzziello1, Laura Vilardo2, Paride Pelucchi3
1National Research Council, Institute of Biomedical Technologies, Bari Unit, 70126 Bari, Italy. nicoletta.nuzziello@gmail.com.
Abstract:
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.
Insights
Six microRNAs (miRNAs) are potential biomarkers for multiple sclerosis (MS) across pediatric and adult patients. These miRNAs and associated transcription factors (TFs) reveal key genetic mechanisms in MS pathogenesis.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) and transcription factors (TFs) are implicated in complex diseases like multiple sclerosis (MS).
- Previous miRNomic profiles were associated with pediatric MS (PedMS) patients.
Purpose of the Study:
- To validate miRNA findings in adult-onset MS (AOMS) patients.
- To identify novel genetic mechanisms and regulatory networks in MS pathogenesis using a combined molecular and computational approach.
Main Methods:
- Analysis of miRNA expression profiles in PedMS and AOMS cohorts.
- Computational screening of miRNA target genes.
- Construction of a miRNA-TF co-regulatory network specific to MS.
Main Results:
- Six miRNAs (miR-320a, miR-125a-5p, miR-652-3p, miR-185-5p, miR-942-5p, miR-25-3p) were significantly upregulated in both PedMS and AOMS patients, suggesting potential circulating biomarkers.
- A comprehensive MS-specific miRNA-TF co-regulatory network was hypothesized, involving key regulators like SP1, RELA, NF-κB, TP53, AR, MYC, HDAC1, and STAT3 targeting 61 genes.
- NF-κB and STAT3 were identified as cooperative regulators of immune response genes and inflammatory cell cross-talk.
Conclusions:
- The identified miRNAs may serve as age-independent circulating biomarkers for MS.
- The study provides insights into the genetic underpinnings of MS through a novel miRNA-TF network.
- Multidisciplinary strategies are essential for understanding MS pathogenesis.
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