Abstract Details

Title Functional analysis of validated miRNAs associated with MS disability

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-005

Objective We aim to explore the functional analysis of the regulated genes and pathways of hsa-miR-25-3p, hsa-miR-486-5p and hsa-miR-320b. Moreover, we plan to evaluate whether the selected miRNAs regulate any of the 28 differentially expressed genes in benign and highly active multiple sclerosis (MS).

Background Previous studies performed in our CLIMB-cohort including patients with MS and validated in external cohorts have shown that hsa-miR-25-3p, hsa-miR-486-5p and hsa-miR-320b are associated with disability in MS. A recent study has reported 28 genes differentially expressed in benign MS (EDSS under or equal to 3) and highly active MS (EDSS over 3).

Design/Methods

The enrichment analysis was performed using mir-Pathv3 (DIANA-tools), which uses KEGG and Gene Ontology Analysis to perform the functional analysis. We determined the target genes using miRtarBasev.8h, a database of experimentally validated miRNA-target interactions.

Results A total of 2010 unique genes were identified as targets. The functional profiling showed that the list of target genes was enriched (FDR corrected p value <0.001) in genes involved in hippo signaling pathway, adherence junction, lysine degradation, cell cycle, viral carcinogenesis, and prion disease, pathways that have been previously related with MS. Among the 28 genes related with MS disability, 3 genes were regulated by the selected miRNA. COX5B and RAB7A were regulated by hsa-miR-25-3p and ATM by 320b.

Conclusions Our exploratory study shows that miRNA hsa-miR-25-3p, hsa-miR-486-5p and hsa-miR-320b regulate COX5B, RAB7A and ATM genes, which have been found to be differentially expressed between benign and highly active multiple sclerosis. Moreover, the three miRNAs are involved in hippo signaling pathway, adherence junction, lysine degradation, cell cycle, viral carcinogenesis and prion disease, pathways that have been related with MS. These data support the functional role of hsa-miR-25-3p, hsa-miR-486-5p and hsa-miR-320b in MS disability and highlight the associated pathways and target genes.

Authors/Disclosures
Hrishikesh A. Lokhande (Brigham and Womens Hospital) PRESENTER	Mr. Lokhande has nothing to disclose.
Alicia Gonzalez-Martinez, MD (Hospital Universitario de La Princesa)	Dr. Gonzalez-Martinez has nothing to disclose.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.

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