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

Abstract

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.

Association of XIST/miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti-phospholipid syndrome and its effect on cell adhesion molecules and inflammatory mediators

“…At the same time, the study suggests that both XIST and miRNA155 could be valuable markers for the prediction of miscarriage events; however, they need further clinical investigations. This is in agreement with preceding studies which document the utility of these noncoding genes as noninvasive accurate, and reproducible, diagnostic and prognostic tools 45 – 47 …”

Diagnostic efficacy of long non-coding RNAs in multiple sclerosis: a systematic review and meta-analysis

“…Subsequent careful screening of abstracts led to the exclusion of 295 articles. Final inclusion criteria—excluding animal cell experiments, non-blood sample studies, data extraction issues, reviews, and comments—resulted in 13 studies ( Gharesouran et al, 2019b ; Sayad et al, 2019 ; Shaker et al, 2019 ; Ghaiad et al, 2020 ; Senousy et al, 2020 ; Safa et al, 2021 ; Soltanmoradi et al, 2021 ; Akbari et al, 2022 ; Amiri et al, 2022 ; Attia et al, 2023 ; Ghafouri-Fard et al, 2023 ; Kamal et al, 2023 ; Kortam et al, 2023 ) qualifying for the meta-analysis. This process is detailed in Figure 1 .…”

Modulating miR-146a Expression by Hydrogen Sulfide Ameliorates Motor Dysfunction and Axonal Demyelination in Cuprizone-Induced Multiple Sclerosis

“…12−14 Therefore, continuous studies are interested in attaining a therapeutic tool that may give promise for alleviating MS symptoms. 15 So, the current study is directed to investigate the effect of hydrogen sulfide (H 2 S) on reversing cuprizone-induced demyelination or stimulating oligodendrocyte-mediated remyelination. H 2 S is a well-known gasotransmitter that has numerous physiological functions.…”

“…miRNAs play an essential role in numerous diseases. − One of the main mechanisms that modulates neuronal remyelination is the production of microRNAs, especially miR-146a, which is known to contribute to repairing demyelinated lesions . Consequently, miR-146a is considered a vital target for different therapeutic approaches in treating MS. Nowadays, there are different treatment strategies for MS; however, none of them provide a complete cure for the disease. − Therefore, continuous studies are interested in attaining a therapeutic tool that may give promise for alleviating MS symptoms . So, the current study is directed to investigate the effect of hydrogen sulfide (H 2 S) on reversing cuprizone-induced demyelination or stimulating oligodendrocyte-mediated remyelination.…”