miR-132-3p, miR-106b-5p, and miR-19b-3p Are Associated with Brain-Derived Neurotrophic Factor Production and Clinical Activity in Multiple Sclerosis: A Pilot Study
Autor: | Fatma Sağır, Erdem Tüzün, Temel Tombul, Recai Turkoglu, Gizem Koral, Nagehan Ersoy Tunali, Vuslat Yilmaz, Selen Çırak |
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Rok vydání: | 2021 |
Předmět: |
Oncology
Adult Male medicine.medical_specialty Down-Regulation Pilot Projects Peripheral blood mononuclear cell Neuroprotection miR-132 Multiple Sclerosis Relapsing-Remitting Neurotrophic factors Internal medicine Medicine Humans Genetics (clinical) Brain-derived neurotrophic factor Expanded Disability Status Scale business.industry Multiple sclerosis Brain-Derived Neurotrophic Factor General Medicine Middle Aged Multiple Sclerosis Chronic Progressive medicine.disease MicroRNAs Real-time polymerase chain reaction Female business |
Zdroj: | Genetic testing and molecular biomarkers. 25(11) |
ISSN: | 1945-0257 |
Popis: | Introduction: Brain-derived neurotrophic factor (BDNF) levels are reduced in advanced stages of multiple sclerosis (MS) and may be associated with reduced regenerative capability in progressive MS. This has brought increased attention to factors regulating BDNF production in MS. Our aim was to investigate the link between neurotrophin-regulating microRNAs (miRNA) and disease progression in MS. Materials and Methods: Serum levels of BDNF and peripheral blood mononuclear cell (PBMC) expression levels of miR-132-3p, miR-106b-5p and miR-19b-3p were respectively measured by ELISA and real time PCR in twelve relapsing remitting MS (RRMS) patients, seven secondary progressive MS (SPMS) patients and fourteen healthy controls. Results: Serum BDNF levels were significantly reduced in SPMS patients, while selected miRNAs were significantly upregulated in PBMC of RRMS and SPMS patients. miR-106b-5p and miR-19b-3p respectively showed the highest sensitivity and specificity for MS diagnosis by receiver operating characteristic curve analysis. There was a negative correlation between levels of BDNF and the miRNAs in RRMS. Likewise, levels of BDNF and the investigated miRNAs showed positive and negative correlations respectively with the expanded disability status scale in RRMS and SPMS patients. miR-132-3p and miR-106b-5p levels showed positive correlations with the progression index in SPMS patients. Conclusion: Our results suggest that increased disability is associated with downregulation of miR-132-3p, miR-106b-5p and miR-19b-3p in RRMS patients and putatively promotes increased production of neuroprotective BDNF as a compensatory mechanism. This link between the investigated miRNAs and BDNF in RRMS does not appears to hold for SPMS. This might be one of the factors contributing to reduced regenerative ability in the progressive stage of MS. |
Databáze: | OpenAIRE |
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