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

Stojanović SD, Fuchs M, Liang C, Schmidt K, Xiao K, Just A, Pfanne A, Pich A, Warnecke G, Braubach P, Petzold C, Jonigk D, Distler J, Fiedler J, Thum T, Kunz M (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 11

Article Number: 12456

Journal Issue: 1

DOI: 10.1038/s41598-021-89531-7

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.

Authors with CRIS profile

Maximilian Fuchs Lehrstuhl für Medizinische Informatik Jörg Distler Professur für Molekulare Mechanismen der Organfibrose Meik Kunz Lehrstuhl für Medizinische Informatik

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

Stojanović, S.D., Fuchs, M., Liang, C., Schmidt, K., Xiao, K., Just, A.,... Kunz, M. (2021). Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-89531-7

MLA:

Stojanović, Stevan D., et al. "Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics." Scientific Reports 11.1 (2021).

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