Multiple Sclerosis: CircRNA Profile Defined Reveals Links to B-Cell Function

Overview

Journal Neurol Neuroimmunol Neuroinflamm

Specialty Neurology

Date 2021 Aug 13

PMID 34385287

Citations 15

Authors

Anna E Zurawska

Marcin P Mycko

Igor Selmaj

Cedric S Raine

Krzysztof W Selmaj

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: To investigate the total circular RNA (circRNA) profile in patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HCs).

Methods: Hybridization microarray was used to define the circRNA profile in peripheral blood mononuclear cells (PBMCs) from 20 untreated patients with RRMS (10 in relapse and 10 in remission) and 10 HCs. We analyzed close to 14,000 individual circRNAs per sample. The discovery set data were validated using quantitative reverse transcription-PCR with an independent cohort of 47 patients with RRMS (19 in relapse and 28 in remission) and 27 HCs.

Results: Microarray analysis revealed 914 transcripts to be differentially expressed between patients with RRMS in relapse and HCs ( < 0.05). We validated 3 circRNAs from 5 showing highest levels of differential expression in the RRMS relapse vs HC group: hsa_circRNA_101348, hsa_circRNA_102611, and hsa_circRNA_104361. Their expression was significantly increased during relapse in RRMS ( = 0.0002, FC = 2.9; = 0.01, FC = 1.6; and = 0.001, FC = 1.5, respectively) and in patients showing gadolinium enhancement on brain MRI (hsa_circRNA_101348, = 0.0039, FC = 2.4; hsa_circRNA_104361, = 0.029, FC = 1.7). Bioinformatic analysis revealed 15 microRNAs interacting with these circRNAs in a complementary manner and led to the discovery and validation of 3 protein-coding RNAs upregulated in patients with RRMS during relapse. Two of these, and , have previously been implicated in B-cell function.

Discussion: circRNAs display a distinct profile in PBMCs from patients with RRMS, and our results may implicate circRNA in the known disturbed B-cell activity in RRMS and thus represent a novel biomarker for monitoring relapse activity.

Citing Articles

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