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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doaj-757334abd2ab4df69064526720aa8b802021-06-20T11:34:19ZengNature Publishing GroupScientific Reports2045-23222021-06-011111910.1038/s41598-021-89531-7Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformaticsStevan D. Stojanović0Maximilian Fuchs1Chunguang Liang2Kevin Schmidt3Ke Xiao4Annette Just5Angelika Pfanne6Andreas Pich7Gregor Warnecke8Peter Braubach9Christina Petzold10Danny Jonigk11Jörg H. W. Distler12Jan Fiedler13Thomas Thum14Meik Kunz15Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical SchoolChair of Medical Informatics, Friedrich-Alexander University (FAU) of Erlangen-NürnbergChair of Medical Informatics, Friedrich-Alexander University (FAU) of Erlangen-NürnbergInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical SchoolInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical SchoolInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical SchoolInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical SchoolInstitute of Toxicology and Core Unit Proteomics, Hannover Medical SchoolDepartment of Cardiac Surgery, University of HeidelbergInstitute of Pathology, Hannover Medical SchoolInstitute of Pathology, Hannover Medical SchoolInstitute of Pathology, Hannover Medical SchoolDepartment of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander University (FAU) of Erlangen-NürnbergInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical SchoolInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical SchoolChair of Medical Informatics, Friedrich-Alexander University (FAU) of Erlangen-NürnbergAbstract 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.https://doi.org/10.1038/s41598-021-89531-7 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-06-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-89531-7 |
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