MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-β Axis: New Clinical Insights.

Autor: Kortam MA; Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Elfar N; School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo 11578, Egypt.; Egyptian Drug Authority (EDA), Ministry of Health and Population, Cairo 11567, Egypt., Shaker OG; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt., El-Boghdady NA; Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Abd-Elmawla MA; Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Jazyk: angličtina
Zdroj: ACS chemical neuroscience [ACS Chem Neurosci] 2023 Mar 15; Vol. 14 (6), pp. 1107-1118. Date of Electronic Publication: 2023 Mar 06.
DOI: 10.1021/acschemneuro.2c00653
Abstrakt: Multiple sclerosis (MS) is a chronic disease and one of the leading causes of disability in young adults. The current study aims to investigate the pathogenesis of MS via studying the regulatory role of novel lncRNA MAGI2-AS3 in miR-374b-5p and their downstream targets PTEN/AKT/IRF-3/IFN-β and the relationship of this pathway with disease severity. Moreover, it aims to assess the role of MAGI2-AS3/miR-374b-5p as diagnostic and/or prognostic biomarkers for MS. Overall, 150 contributors were recruited: 100 patients with MS and 50 healthy volunteers. Gene expression of MAGI2-AS3, miR-374b-5p, PTEN, AKT, and IRF-3 were assessed using RT-qPCR, and IFN-β was measured by ELISA. Compared with the healthy control group, serum MAGI2-AS3 and PTEN were downregulated in MS patients, whereas miR-374b-5p, PI3K, AKT, IRF-3, and IFN-β were upregulated in MS patients. Furthermore, MAGI2-AS3 was downregulated, while miR-374b-5p was upregulated in MS patients with an expanded disability status scale (EDSS) ≥3.5, compared to patients with an EDSS <3.5. Receiver-operating-characteristic curve analysis revealed that MAGI2-AS3 and miR-374b-5p can be used in the diagnosis of MS. Remarkably, multivariate logistic analysis revealed that MAGI2-AS3, miR-374b-5p, PTEN, and AKT act as independent variables in MS. Moreover, MAGI2-AS3 was directly correlated with PTEN and inversely correlated with miR-374b-5p, AKT, and EDSS. Regarding miR-374b-5p, it was positively correlated with AKT and EDSS. In conclusion, the study showed for the first time that the crosstalk between MAGI2-AS3 and miR-374b-5p could affect the AKT/IRF3/IFN-β axis in MS. Interestingly, MAGI2-AS3 and miR-374b-5p could be genetic noninvasive biomarkers for MS.
Databáze: MEDLINE