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

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 characterizati...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2021-06, Vol.11 (1), p.12456-12456, Article 12456
Main Authors: Stojanović, Stevan D., Fuchs, Maximilian, Liang, Chunguang, Schmidt, Kevin, Xiao, Ke, Just, Annette, Pfanne, Angelika, Pich, Andreas, Warnecke, Gregor, Braubach, Peter, Petzold, Christina, Jonigk, Danny, Distler, Jörg H. W., Fiedler, Jan, Thum, Thomas, Kunz, Meik
Format: Article
Language:English
Subjects:
631/114
692/420
692/699
Bioinformatics
Computer programs
Data mining
Fibroblasts
Fibrosis
Humanities and Social Sciences
Lung diseases
miRNA
Molecular modelling
multidisciplinary
Pulmonary fibrosis
Ribonucleic acid
RNA
RNA-binding protein
Science
Science (multidisciplinary)
Sequence analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-89531-7