Abstract
BackgroundNon-coding small RNA molecules play pivotal roles in cellular and developmental processes by regulating gene expression at the post-transcriptional level. In human diseases, the roles of the non-coding small RNAs in specific degradation or translational suppression of the targeted mRNAs suggest a potential therapeutic approach of post-transcriptional gene silencing that targets the underlying disease etiology. The involvement of non-coding small RNAs in the pathogenesis of neurodegenerative diseases such as Alzheimer’s , Parkinson’s disease and Multiple Sclerosis has been demonstrated. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by chronic inflammation, demyelination and scarring as well as a broad spectrum of signs and symptoms. The current standard treatment for SM is interferon ß (IFNß) that is less than ideal due to side effects. In this study we administered the standard IFN-ß treatment to Relapsing-Remitting MS patients, all responder to the therapy; then examined their sncRNA expression profiles in order to identify the ncRNAs that were associated with MS patients’ response to IFNß.Methods40 IFNß treated Relapsing-Remitting MS patients were enrolled. We analyzed the composition of the entire small transcriptome by a small RNA cloning method, using peripheral blood from Relapsing-Remitting MS patients at baseline and 3 and 6 months after the start of IFNß therapy. Real-time qPCR from the same patients group and from 20 additional patients was performed to profile miRNAs expression.ResultsBeside the altered expression of several miRNAs, our analyses revealed the differential expression of small nucleolar RNAs and misc-RNAs.For the first time, we found that the expression level of miR-26a-5p changed related to INF-β response. MiR-26a-5p expression was significantly higher in IFN-β treated RRMS patients at 3 months treatment, keeping quite stable at 6 months treatments.ConclusionsOur results might provide insights into the mechanisms of action of IFN-β treatment in MS and provide fundamentals for the development of new biomarkers and/or therapeutic tools.
Highlights
Non-coding small RNA molecules play pivotal roles in cellular and developmental processes by regulating gene expression at the post-transcriptional level
About 1000 cloned Small noncoding RNAs (sncRNAs) molecules were independently sequenced for each library
This approach allowed us to obtain a profile of sncRNAs expressed in these cell types at different treatment stages (Figure 1)
Summary
Non-coding small RNA molecules play pivotal roles in cellular and developmental processes by regulating gene expression at the post-transcriptional level. The roles of the non-coding small RNAs in specific degradation or translational suppression of the targeted mRNAs suggest a potential therapeutic approach of post-transcriptional gene silencing that targets the underlying disease etiology. The involvement of non-coding small RNAs in the pathogenesis of neurodegenerative diseases such as Alzheimer’s , Parkinson’s disease and Multiple Sclerosis has been demonstrated. Small noncoding RNAs (sncRNAs) are essential post-transcriptional gene regulation elements that are critical to immune system and neurodegenerative diseases [3,4,5] by affecting mRNA stability and the expression of multiple genes. Better understanding of miRNA and sncRNAs role in MS development and treatment, might contribute to the accumulation of data to understand MS pathogenesis as well as potential approaches for new therapeutic managing
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