miR-181a-5p is a potential candidate epigenetic biomarker in multiple sclerosis
Tuba Gökdoğan Edgünlü1, Şenay Görücü Yılmaz2, Ufuk Emre3
1Department of Medical Biology, Medical Faculty, Muğla Sıtkı Koçman University, Muğla, Turkey.
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 (miRNAs) plays an important role in MS pathology. In this cohort study, differential expression of the four miRNAs (hsa-miR-155-5p, hsa-miR-9-5p, hsa-miR-181a-5p, and hsa-miR-125b-5p) was 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 analyses revealed possible genes and pathways specific to miRNAs. Peripheral blood miRNA expressions were detected by quantitative real-time PCR (qPCR). hsa-miR-181a-5p 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 analyses showed that hsa-miR-181a-5p may participate in MS pathology by targeting MAP2K1, CREB1, ATXN1, and ATXN3 genes in inflammation and neurodegeneration pathways. The circulatory hsa-miR-181a-5p 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 for therapeutic purpose.
Insights
Downregulated hsa-miR-181a-5p is linked to increased multiple sclerosis (MS) risk. This microRNA may serve as a diagnostic and therapeutic tool for MS by targeting key disease pathways.
Area of Science:
- Neuroimmunology
- Epigenetics
- Molecular Biology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) inflammatory disease.
- MicroRNAs (miRNAs) show abnormal expression patterns in MS pathology.
- Understanding miRNA roles is crucial for MS diagnosis and treatment.
Purpose of the Study:
- To investigate differential expression of four specific miRNAs in MS patients and healthy controls.
- To identify potential miRNA targets and pathways involved in MS pathogenesis.
- To evaluate the diagnostic and therapeutic potential of circulating miRNAs in MS.
Main Methods:
- Cohort study involving 39 MS patients (RRMS and SPMS) and 30 healthy controls.
- Quantitative real-time PCR (qPCR) to detect peripheral blood miRNA expression.
- In silico analyses to predict miRNA-specific genes and pathways.
Main Results:
- hsa-miR-181a-5p was significantly downregulated in MS patients (P=0.012), correlating with increased MS risk.
- Three other miRNAs (hsa-miR-155-5p, hsa-miR-9-5p, hsa-miR-125b-5p) were upregulated but not significantly associated with MS (P<0.05).
- The diagnostic accuracy (AUC) for distinguishing MS was 0.779. In silico analysis suggested hsa-miR-181a-5p targets genes in inflammation and neurodegeneration pathways.
Conclusions:
- Circulating hsa-miR-181a-5p may play a role in MS pathogenesis by regulating inflammation and neurodegeneration.
- hsa-miR-181a-5p demonstrates potential as an epigenomic biomarker for MS diagnosis.
- This miRNA could be a future therapeutic target for reversing MS-related pathological mechanisms.
