Transcriptome regulation network in Multiple sclerosis: Role of circular RNAs.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, that leads to neurological disability. The disease course and clinical phenotype are highly variable and therefore, biomarkers that can aid in the clinical practice are needed. Previous studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers thanks to the features endowed by their circularity. In this thesis, we have performed different approaches to characterise the circRNA expression in leukocytes, peripheral blood mononuclear cells and extracellular vesicles from MS patients. Results have revealed hundreds of circRNAs whose expression is changed in the disease, and we have proposed eleven of them as potential minimally-invasive biomarkers. Finally, our functional experiments indicate that circRNAs may act as regulators of the immune response. This thesis opens a new research line in MS for future investigations to further evaluate the biomarker potential and the function of circRNAs in MS.