Identification of novel genetic regulations associated with airway epithelial homeostasis using next-generation sequencing data and bioinformatics approaches

Abstract

Airway epithelial cells play important roles in airway remodeling. Understanding gene regulations in airway epithelial homeostasis may provide new insights into pathogenesis and treatment of asthma. This study aimed to combine gene expression (GE) microarray, next generation sequencing (NGS), and bioinformatics to explore genetic regulations associated with airway epithelial homeostasis. We analyzed expression profiles of mRNAs (GE microarray) and microRNAs (NGS) in normal and asthmatic bronchial epithelial cells, and identified 9 genes with potential microRNA-mRNA interactions. Of these 9 dysregulated genes, downregulation of MEF2C and MDGA1 were validated in a representative microarray (GSE43696) from the gene expression omnibus (GEO) database. Our findings suggested that upregulated mir-203a may repress MEF2C, a transcription factor, leading to decreased cellular proliferation. In addition, upregulated mir-3065-3p may repress MDGA1, a cell membrane anchor protein, resulting in suppression of cell-cell adhesion. We also found that KCNJ2, a potassium channel, was downregulated in severe asthma and may promote epithelial cell apoptosis. We proposed that aberrant regulations of mir-203a-MEF2C and mir-3065-3p-MDGA1, as well as downregulation of KCNJ2, play important roles in airway epithelial homeostasis in asthma. These findings provide new perspectives on diagnostic or therapeutic strategies targeting bronchial epithelium for asthma. The approach in this study also provides a new aspect of studying asthma.