Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts

Abstract Familial Mediterranean fever (FMF); is an autosomal recessively inherited autoinflammatory disease caused by the mutations in the Mediterranean Fever (MEFV) gene. Recent studies have shown that epigenetic control mechanisms, particularly non-coding RNAs, may play a role in the pathogenesis...

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Autores principales:	Yeliz Z. Akkaya-Ulum, Tayfun Hilmi Akbaba, Zeynep Tavukcuoglu, Jae Jin Chae, Engin Yilmaz, Seza Ozen, Banu Balci-Peynircioglu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb33032f28b04874b0a8409ccf3ecf90
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spelling	oai:doaj.org-article:bb33032f28b04874b0a8409ccf3ecf902021-12-02T14:12:42ZFamilial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts10.1038/s41598-020-80097-42045-2322https://doaj.org/article/bb33032f28b04874b0a8409ccf3ecf902021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80097-4https://doaj.org/toc/2045-2322Abstract Familial Mediterranean fever (FMF); is an autosomal recessively inherited autoinflammatory disease caused by the mutations in the Mediterranean Fever (MEFV) gene. Recent studies have shown that epigenetic control mechanisms, particularly non-coding RNAs, may play a role in the pathogenesis of autoinflammation. microRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression at the post-transcriptional level. The phenotypic heterogeneity of FMF disease suggests that FMF may not be a monogenic disease, suggesting that epigenetic factors may affect phenotypic presentation. Here we examined the potential anti-inflammatory effect of miR-197-3p, which is a differentially expressed miRNA in FMF patients, by using inflammation related functional assays. We monitored gene expression levels of important cytokines, as well as performed functional studies on IL-1β secretion, caspase-1 activation, apoptosis assay, and cell migration assay. These experiments were used to evaluate the different stages of inflammation following pre-miR-197 transfection. Anti-miR-197 transfections were performed to test the opposite effect. 3′UTR luciferase activity assay was used for target gene studies. Our results obtained by inflammation-related functional assays demonstrated an anti-inflammatory effect of miR-197-3p in different cell types (synovial fibroblasts, monocytes, macrophages). 3′UTR luciferase activity assay showed that miR-197-3p directly binds to the interleukin-1beta (IL-1β) receptor, type I (IL1R1) gene, which is one of the key molecules of the inflammatory pathways. This study may contribute to understand the role of miR-197-3p in autoinflammation process. Defining the critical miRNAs may guide the medical community in a more personalized medicine in autoinflammatory diseases.Yeliz Z. Akkaya-UlumTayfun Hilmi AkbabaZeynep TavukcuogluJae Jin ChaeEngin YilmazSeza OzenBanu Balci-PeynirciogluNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yeliz Z. Akkaya-Ulum Tayfun Hilmi Akbaba Zeynep Tavukcuoglu Jae Jin Chae Engin Yilmaz Seza Ozen Banu Balci-Peynircioglu Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts
description	Abstract Familial Mediterranean fever (FMF); is an autosomal recessively inherited autoinflammatory disease caused by the mutations in the Mediterranean Fever (MEFV) gene. Recent studies have shown that epigenetic control mechanisms, particularly non-coding RNAs, may play a role in the pathogenesis of autoinflammation. microRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression at the post-transcriptional level. The phenotypic heterogeneity of FMF disease suggests that FMF may not be a monogenic disease, suggesting that epigenetic factors may affect phenotypic presentation. Here we examined the potential anti-inflammatory effect of miR-197-3p, which is a differentially expressed miRNA in FMF patients, by using inflammation related functional assays. We monitored gene expression levels of important cytokines, as well as performed functional studies on IL-1β secretion, caspase-1 activation, apoptosis assay, and cell migration assay. These experiments were used to evaluate the different stages of inflammation following pre-miR-197 transfection. Anti-miR-197 transfections were performed to test the opposite effect. 3′UTR luciferase activity assay was used for target gene studies. Our results obtained by inflammation-related functional assays demonstrated an anti-inflammatory effect of miR-197-3p in different cell types (synovial fibroblasts, monocytes, macrophages). 3′UTR luciferase activity assay showed that miR-197-3p directly binds to the interleukin-1beta (IL-1β) receptor, type I (IL1R1) gene, which is one of the key molecules of the inflammatory pathways. This study may contribute to understand the role of miR-197-3p in autoinflammation process. Defining the critical miRNAs may guide the medical community in a more personalized medicine in autoinflammatory diseases.
format	article
author	Yeliz Z. Akkaya-Ulum Tayfun Hilmi Akbaba Zeynep Tavukcuoglu Jae Jin Chae Engin Yilmaz Seza Ozen Banu Balci-Peynircioglu
author_facet	Yeliz Z. Akkaya-Ulum Tayfun Hilmi Akbaba Zeynep Tavukcuoglu Jae Jin Chae Engin Yilmaz Seza Ozen Banu Balci-Peynircioglu
author_sort	Yeliz Z. Akkaya-Ulum
title	Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts
title_short	Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts
title_full	Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts
title_fullStr	Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts
title_full_unstemmed	Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts
title_sort	familial mediterranean fever-related mir-197-3p targets il1r1 gene and modulates inflammation in monocytes and synovial fibroblasts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bb33032f28b04874b0a8409ccf3ecf90
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Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts

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