The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis.

Georgia Mandolesi,Francesca De Vito,Sara Balletta,Fabio Buttari,Mario Stampanoni Bassi,Livia Guadalupi,Antonio Bruno,Roberto Furlan,Valentina Vanni,Diego Fresegna,Valerio Licursi,Annamaria Finardi,Chiara Castelli,Antonietta Gentile,Alessandra Musella,Monica Nencini,Silvia Caioli,Francesca Romana Rizzo,Krizia Sanna,Diego Centonze,Carlo Presutti,Ettore Dolcetti,Francesca De Santa,Silvia Bullitta,Luana Gilio,Alessandro Moscatelli,Colleen P Ryan

doi:10.3390/cells10020330

Abstract

The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation. Additionally, we found that the CSF let-7b-5p levels were significantly reduced in patients with the progressive MS compared to patients with relapsing-remitting MS and were negatively correlated with characteristic hallmark processes of the two phases of the disease. Indeed, in the non-progressive phase, let-7b-5p inversely associated with both central and peripheral inflammation; whereas, in progressive MS, the CSF levels of let-7b-5p negatively correlated with clinical disability at disease onset and after a follow-up period. Overall, our results uncovered, by the means of a multidisciplinary approach and multiple statistical analyses, a new possible pleiotropic action of let-7b-5p in MS, with potential utility as a biomarker of MS course.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS), characterized by a highly variable relapse rate and a progressive increase of clinical disability
The Let-7 Family Regulates Crucial Processes Involved in multiple sclerosis (MS) Pathophysiology. Both the sequences of miRNAs grouped in the let-7 family and their genomic organization are highly conserved among vertebrates [14]
Considering that Gene Ontology (GO) analysis revealed 18 experimental validated target mRNAs of let-7 family involved in miRNA metabolism, we evaluated the possible crosstalk between let-7 miRNAs and MS-linked miRNAs circulating in the cerebrospinal fluid (CSF)

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS), characterized by a highly variable relapse rate and a progressive increase of clinical disability. The inflammatory events are typical in the relapsing-remitting (RRMS) phase of the disease, during which there is a full or partial recovery of clinical symptoms until reaching a phase of irreversible progressive worsening of the disease (i.e., secondary progressive MS, SPMS). A small number of patients with MS enter directly into the progressive phase after clinical onset (i.e., primary progressive MS, PPMS) due to irreversible accumulation of neurological disabilities as a result of axonal injury and neuronal loss [3]

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