Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics

Abstract The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the chara...

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Autores principales:	Stevan D. Stojanović, Maximilian Fuchs, Chunguang Liang, Kevin Schmidt, Ke Xiao, Annette Just, Angelika Pfanne, Andreas Pich, Gregor Warnecke, Peter Braubach, Christina Petzold, Danny Jonigk, Jörg H. W. Distler, Jan Fiedler, Thomas Thum, Meik Kunz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/757334abd2ab4df69064526720aa8b80
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spelling	oai:doaj.org-article:757334abd2ab4df69064526720aa8b802021-12-02T16:04:30ZReconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics10.1038/s41598-021-89531-72045-2322https://doaj.org/article/757334abd2ab4df69064526720aa8b802021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89531-7https://doaj.org/toc/2045-2322Abstract The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.Stevan D. StojanovićMaximilian FuchsChunguang LiangKevin SchmidtKe XiaoAnnette JustAngelika PfanneAndreas PichGregor WarneckePeter BraubachChristina PetzoldDanny JonigkJörg H. W. DistlerJan FiedlerThomas ThumMeik KunzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stevan D. Stojanović Maximilian Fuchs Chunguang Liang Kevin Schmidt Ke Xiao Annette Just Angelika Pfanne Andreas Pich Gregor Warnecke Peter Braubach Christina Petzold Danny Jonigk Jörg H. W. Distler Jan Fiedler Thomas Thum Meik Kunz Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
description	Abstract The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.
format	article
author	Stevan D. Stojanović Maximilian Fuchs Chunguang Liang Kevin Schmidt Ke Xiao Annette Just Angelika Pfanne Andreas Pich Gregor Warnecke Peter Braubach Christina Petzold Danny Jonigk Jörg H. W. Distler Jan Fiedler Thomas Thum Meik Kunz
author_facet	Stevan D. Stojanović Maximilian Fuchs Chunguang Liang Kevin Schmidt Ke Xiao Annette Just Angelika Pfanne Andreas Pich Gregor Warnecke Peter Braubach Christina Petzold Danny Jonigk Jörg H. W. Distler Jan Fiedler Thomas Thum Meik Kunz
author_sort	Stevan D. Stojanović
title	Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
title_short	Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
title_full	Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
title_fullStr	Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
title_full_unstemmed	Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
title_sort	reconstruction of the mir-506-quaking axis in idiopathic pulmonary fibrosis using integrative multi-source bioinformatics
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/757334abd2ab4df69064526720aa8b80
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Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics

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