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

• Published in: PloS one 2022-10, Vol.17 (10), p.e0271262-e0271262
• Main Authors: Shaik, Noor Ahmad, Nasser, Khalidah, Mohammed, Arif, Mujalli, Abdulrahman, Obaid, Ahmad A, El-Harouni, Ashraf A, Elango, Ramu, Banaganapalli, Babajan
• Format: Article
• Language: English
• Subjects: Analysis; Asthma; Biology; Biology and life sciences; Biomarkers; Care and treatment; Cell differentiation; Chronic obstructive pulmonary disease; Computer applications; Datasets; Development and progression; Differentiation (biology); DNA binding proteins; Epithelial cells; Epithelium; FOXO1 protein; Gene expression; Genes; Genetic aspects; Global health; Health aspects; Helper cells; Identification and classification; Interleukin 17; Lung diseases; Lymphocytes T; Medicine and Health Sciences; Messenger RNA; MicroRNA; MicroRNAs; miRNA; Pathogenesis; Public health; Respiratory tract; Sox9 protein; Target detection; Transcription factors; Transcriptomics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0271262

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.