miR-181a-5p is a potential candidate epigenetic biomarker in multiple sclerosis

Abstract

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Abnormal expression of microRNAs (miRNA) plays an important role in MS pathology. In this cohort study, differential expression of the four miRNAs (<i>hsa-miR-155-5p</i>, <i>hsa-miR-9-5p</i>, <i>hsa-miR-181a-5p</i>, and <i>hsa-miR-125b-5p</i>) were investigated in 69 individuals, including 39 MS patients (relapsing-remitting MS (RRMS), n = 27; secondary progressive MS (SPMS), n = 12) and 30 healthy controls. In silico analyzes revealed possible genes and pathways specific to miRNAs. Peripheral blood miRNA expressions were detected by quantitative Real-Time PCR (qPCR). <i>hsa-miR-181a-5p</i> was downregulated and associated with increased MS risk (P = 0.012). The other three miRNAs were upregulated and not associated with MS (P < 0.05). The area under the curve (AUC) is 0.779. In silico analyzes showed that <i>hsa-miR-181a-5p</i> may participate in MS pathology by targeting<i> MAP2K1</i>, <i>CREB1</i>, <i>ATXN1</i>, and <i>ATXN3</i> genes in inflammation and neurodegeneration pathways. The circulatory <i>hsa-miR-181a-5p</i> can regulate target genes, reversing the mechanisms involved in MS pathologies such as protein uptake and processing, cell proliferation and survival, inflammation, and neurodegeneration. Thus, this miRNA could be used as an epigenomic-guided diagnostic tool and therapeutic.

Integrated transcriptomics of multiple sclerosis peripheral blood mononuclear cells identified COPG1, RPN1, and KDM3B as potential biomarkers

“…The current body of literature demonstrates the altered expression of the miR-181 family in neurodegenerative disorders, including MS, Parkinson's disease, and Alzheimer's disease (32). Quantitative real-time PCR (qPCR) of PBMCs identi ed miR-181a-5p and miR-181b-5p as differentially downregulated and upregulated miRNAs, respectively, in MS patients (33,34). Moreover, targeting genes involved in neuroin ammation, such as MAP2K1, CREB1, ATXN1, and ATXN3, by miR-181a-5p re ects its therapeutic potential (34).…”

“…Quantitative real-time PCR (qPCR) of PBMCs identi ed miR-181a-5p and miR-181b-5p as differentially downregulated and upregulated miRNAs, respectively, in MS patients (33,34). Moreover, targeting genes involved in neuroin ammation, such as MAP2K1, CREB1, ATXN1, and ATXN3, by miR-181a-5p re ects its therapeutic potential (34). The expression of miR-181c-5p is reported to be misregulated in PBMCs, cerebrospinal uid (CSF), and serum of relapsing-remitting multiple sclerosis (RRMS) patients (35).…”

Remyelination in multiple sclerosis from the miRNA perspective

“…Furthermore, ROC analysis allowed distinguishing RRMS from SPMS/PPMS patients with AUC values for miR-433-3p, miR-432-5p, and miR-485-5p were 0.93, 0.86, and 0.87, respectively ( Ebrahimkhani et al, 2017 ). The recent study by Edgünlü et al (2022) showed that the expression of miR-181a-5p was downregulated and associated with an increased risk of MS ( p = 0.012). Furthermore, in silico analyses showed that circulating miR-181a-5p can participate in MS pathology by targeting genes involved in inflammation and neurodegeneration molecular pathways, such as MAP2K1, CREB1, ATXN1, and ATXN3 ( Edgünlü et al, 2022 ).…”

“…The recent study by Edgünlü et al (2022) showed that the expression of miR-181a-5p was downregulated and associated with an increased risk of MS ( p = 0.012). Furthermore, in silico analyses showed that circulating miR-181a-5p can participate in MS pathology by targeting genes involved in inflammation and neurodegeneration molecular pathways, such as MAP2K1, CREB1, ATXN1, and ATXN3 ( Edgünlü et al, 2022 ).…”