MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis

Davide Lecca, Davide Marangon, Giusy T. Coppolino, Aida Menéndez Méndez, Annamaria Finardi, Gloria Dalla Costa, Vittorio Martinelli, Roberto Furlan, Maria P. Abbracchio

Research output: Contribution to journalArticle

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Abstract

In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS). Here, we identify miR-125a-3p, a developmentally regulated miRNA, as a new actor of oligodendroglial maturation, that, in the mammalian CNS regulates the expression of myelin genes by simultaneously acting on several of its already validated targets. In cultured OPCs, over-expression of miR-125a-3p by mimic treatment impairs while its inhibition with an antago-miR stimulates oligodendroglial maturation. Moreover, we show that miR-125a-3p levels are abnormally high in the cerebrospinal fluid of MS patients bearing active demyelinating lesions, suggesting that its pathological upregulation may contribute to MS development, at least in part by blockade of OPC differentiation leading to impaired repair of demyelinated lesions.

Original languageEnglish
Article number34503
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Oct 4 2016

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Multiple Sclerosis
Myelin Sheath
MicroRNAs
Central Nervous System
Small Untranslated RNA
Oligodendroglia
Epigenomics
Axons
Cerebrospinal Fluid
Transcription Factors
Up-Regulation
Gene Expression
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Lecca, D., Marangon, D., Coppolino, G. T., Méndez, A. M., Finardi, A., Costa, G. D., ... Abbracchio, M. P. (2016). MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. Scientific Reports, 6, [34503]. https://doi.org/10.1038/srep34503

MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. / Lecca, Davide; Marangon, Davide; Coppolino, Giusy T.; Méndez, Aida Menéndez; Finardi, Annamaria; Costa, Gloria Dalla; Martinelli, Vittorio; Furlan, Roberto; Abbracchio, Maria P.

In: Scientific Reports, Vol. 6, 34503, 04.10.2016.

Research output: Contribution to journalArticle

Lecca, Davide ; Marangon, Davide ; Coppolino, Giusy T. ; Méndez, Aida Menéndez ; Finardi, Annamaria ; Costa, Gloria Dalla ; Martinelli, Vittorio ; Furlan, Roberto ; Abbracchio, Maria P. / MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. In: Scientific Reports. 2016 ; Vol. 6.
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