Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients

Tayfun Hilmi Akbaba, Yeliz Z. Akkaya-Ulum, Ezgi Deniz Batu, Federica Penco, Helmut Wittkowski, Benjamin Kant, Marielle E. van Gijn, Dirk Foell, Marco Gattorno, Seza Ozen, Banu Balci-Peynircioglu*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    4 Citaten (Scopus)
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    Samenvatting

    Abstract: Autoinflammation is the standard mechanism seen in systemic autoinflammatory disease (SAID) patients. This study aimed to investigate the effect of a candidate miRNA, miR-30e-3p, which was identified in our previous study, on the autoinflammation phenotype seen in SAID patients and to analyze its expression in a larger group of European SAID patients. We examined the potential anti-inflammatory effect of miR-30e-3p, which we had defined as one of the differentially expressed miRNAs in microarray analysis involved in inflammation-related pathways. This study validated our previous microarray results of miR-30e-3p in a cohort involving European SAID patients. We performed cell culture transfection assays for miR-30e-3p. Then, in transfected cells, we analyzed expression levels of pro-inflammatory genes; IL-1β, TNF-α, TGF-β, and MEFV. We also performed functional experiments, caspase-1 activation by fluorometric assay kit, apoptosis assay by flow cytometry, and cell migration assays by wound healing and filter system to understand the possible effect of miR-30e-3p on inflammation. Following these functional assays, 3'UTR luciferase activity assay and western blotting were carried out to identify the target gene of the aforementioned miRNA. MiR-30e-3p was decreased in severe European SAID patients like the Turkish patients. The functional assays associated with inflammation suggested that miR-30e-3p has an anti-inflammatory effect. 3'UTR luciferase activity assay demonstrated that miR-30e-3p directly binds to interleukin-1-beta (IL-1β), one of the critical molecules of inflammatory pathways, and reduces both RNA and protein levels of IL-1β. miR-30e-3p, which has been associated with IL-1β, a principal component of inflammation, might be of potential diagnostic and therapeutic value for SAIDs. 

    Key Messages: 

    miR-30e-3p, which targets IL-1β, could have a role in the pathogenesis of SAID patients.

    miR-30e-3p has a role in regulating inflammatory pathways like migration, caspase-1 activation.

    miR-30e-3p has the potential to be used for future diagnostic and therapeutic approaches.

    Originele taal-2English
    Pagina's (van-tot)757-766
    Aantal pagina's10
    TijdschriftJournal of Molecular Medicine
    Volume101
    Nummer van het tijdschrift6
    DOI's
    StatusPublished - jun.-2023

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