Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:101 |
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| Enthalten in: |
Journal of molecular medicine (Berlin, Germany) - 101(2023), 6 vom: 22. Juni, Seite 757-766 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Akbaba, Tayfun Hilmi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.06.2023 Date Revised 03.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00109-023-02327-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357153383 |
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| 245 | 1 | 0 | |a Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients |
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| 520 | |a © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Familial Mediterranean fever | |
| 650 | 4 | |a IL-1β | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a MicroRNA | |
| 650 | 4 | |a Systemic autoinflammatory disease | |
| 650 | 4 | |a miR-30e-3p | |
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| 650 | 7 | |a Luciferases |2 NLM | |
| 650 | 7 | |a EC 1.13.12.- |2 NLM | |
| 650 | 7 | |a Caspases |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
| 650 | 7 | |a MEFV protein, human |2 NLM | |
| 650 | 7 | |a Pyrin |2 NLM | |
| 700 | 1 | |a Akkaya-Ulum, Yeliz Z |e verfasserin |4 aut | |
| 700 | 1 | |a Batu, Ezgi Deniz |e verfasserin |4 aut | |
| 700 | 1 | |a Penco, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Wittkowski, Helmut |e verfasserin |4 aut | |
| 700 | 1 | |a Kant, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a van Gijn, Marielle E |e verfasserin |4 aut | |
| 700 | 1 | |a Foell, Dirk |e verfasserin |4 aut | |
| 700 | 1 | |a Gattorno, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Ozen, Seza |e verfasserin |4 aut | |
| 700 | 1 | |a Balci-Peynircioglu, Banu |e verfasserin |4 aut | |
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