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

Author:

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

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.

Funder

Fondazione Italiana Sclerosi Multipla

Ministero dell’Istruzione, dell’Università e della Ricerca

Ministero della Salute

IRCCS San Raffaele Pisana

Publisher

MDPI AG

Subject

General Medicine

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