Identification of miRNA-mRNA-TFs regulatory network and crucial pathways involved in asthma through advanced systems biology approaches

Noor Ahmad Shaik; Khalidah Nasser; Arif Mohammed; Abdulrahman Mujalli; Ahmad A Obaid; Ashraf A El-Harouni; Ramu Elango; Babajan Banaganapalli

doi:10.1371/journal.pone.0271262

Identification of miRNA-mRNA-TFs regulatory network and crucial pathways involved in asthma through advanced systems biology approaches

PLoS One. 2022 Oct 20;17(10):e0271262. doi: 10.1371/journal.pone.0271262. eCollection 2022.

Authors

Noor Ahmad Shaik^{1

2}, Khalidah Nasser^{2

3}, Arif Mohammed⁴, Abdulrahman Mujalli⁵, Ahmad A Obaid⁵, Ashraf A El-Harouni¹, Ramu Elango^{1

2}, Babajan Banaganapalli^{1

2}

Affiliations

¹ Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
² Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Biology, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
⁵ Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia.

Abstract

Asthma is a life-threatening and chronic inflammatory lung disease that is posing a true global health challenge. The genetic basis of the disease is fairly well examined. However, the molecular crosstalk between microRNAs (miRNAs), target genes, and transcription factors (TFs) networks and their contribution to disease pathogenesis and progression is not well explored. Therefore, this study was aimed at dissecting the molecular network between mRNAs, miRNAs, and TFs using robust computational biology approaches. The transcriptomic data of bronchial epithelial cells of severe asthma patients and healthy controls was studied by different systems biology approaches like differentially expressed gene detection, functional enrichment, miRNA-target gene pairing, and mRNA-miRNA-TF molecular networking. We detected the differential expression of 1703 (673 up-and 1030 down-regulated) genes and 71 (41 up-and 30 down-regulated) miRNAs in the bronchial epithelial cells of asthma patients. The DEGs were found to be enriched in key pathways like IL-17 signaling (KEGG: 04657), Th1 and Th2 cell differentiation (KEGG: 04658), and the Th17 cell differentiation (KEGG: 04659) (p-values = 0.001). The results from miRNAs-target gene pairs-transcription factors (TFs) have detected the key roles of 3 miRs (miR-181a-2-3p; miR-203a-3p; miR-335-5p), 6 TFs (TFAM, FOXO1, GFI1, IRF2, SOX9, and HLF) and 32 miRNA target genes in eliciting autoimmune reactions in bronchial epithelial cells of the respiratory tract. Through systemic implementation of comprehensive system biology tools, this study has identified key miRNAs, TFs, and miRNA target gene pairs as potential tissue-based asthma biomarkers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asthma* / genetics
Biomarkers
Computational Biology / methods
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Interleukin-17 / metabolism
MicroRNAs* / genetics
MicroRNAs* / metabolism
RNA, Messenger / genetics
Systems Biology
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

MicroRNAs
RNA, Messenger
Interleukin-17
Transcription Factors
Biomarkers

Grants and funding

Deanship of Scientific Research (DSR) at King Abdulaziz University, under Grant no G-296-140-1441. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.