A Potential circRNA-miRNA-mRNA Regulatory Network in Asthmatic Airway Epithelial Cells Identified by Integrated Analysis of Microarray Datasets

Background: Asthma is one of the most prevalent chronic respiratory diseases worldwide. Bronchial epithelial cells play a critical role in the pathogenesis of asthma. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges to regulate downstream gene expression. However, the role of epithelial circRNAs in asthma remains to be investigated. This study aims to explore the potential circRNA-miRNA-messenger RNA (mRNA) regulatory network in asthma by integrated analysis of publicly available microarray datasets.Methods: Five mRNA microarray datasets derived from bronchial brushing samples from asthma patients and control subjects were downloaded from the Gene Expression Omnibus (GEO) database. The robust rank aggregation (RRA) method was used to identify robust differentially expressed genes (DEGs) in bronchial epithelial cells between asthma patients and controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to annotate the functions of the DEGs. Protein-protein interaction (PPI) analysis was performed to identify hub genes. Three miRNA databases (Targetscan, miRDB, and miRWalk) were used to predict the miRNAs which potentially target the hub genes. A miRNA microarray dataset derived from bronchial brushings was used to validate the miRNA-mRNA relationships. Finally, a circRNA-miRNA-mRNA network was constructed via the ENCORI database.Results: A total of 127 robust DEGs in bronchial epithelial cells between steroid-naïve asthma patients (n = 272) and healthy controls (n = 165) were identified from five mRNA microarray datasets. Enrichment analyses showed that DEGs were mainly enriched in several biological processes related to asthma, including humoral immune response, salivary secretion, and IL-17 signaling pathway. Nineteen hub genes were identified and were used to construct a potential epithelial circRNA-miRNA-mRNA network. The top 10 competing endogenous RNAs were hsa_circ_0001585, hsa_circ_0078031, hsa_circ_0000552, hsa-miR-30a-3p, hsa-miR-30d-3p, KIT, CD69, ADRA2A, BPIFA1, and GGH.Conclusion: Our study reveals a potential role for epithelial circRNA-miRNA-mRNA network in the pathogenesis of asthma.

Download Full-text

Interleukin-8 gene expression in human bronchial epithelial cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)55037-7 ◽

1991 ◽

Vol 266 (29) ◽

pp. 19611-19617

Author(s):

H. Nakamura ◽

K. Yoshimura ◽

H.A. Jaffe ◽

R.G. Crystal

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Bronchial Epithelial Cells ◽

Interleukin 8 ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial

Download Full-text

Gene Expression of Primary Human Bronchial Epithelial Cells in Response to Coal Dusts with Different Prevalence of Coal Workers' Pneumoconiosis

Journal of Toxicology and Environmental Health Part A ◽

10.1080/15287390306411 ◽

2003 ◽

Vol 66 (13) ◽

pp. 1249-1265 ◽

Cited By ~ 11

Author(s):

Wenwei Hu ◽

Qi Zhang ◽

Wei Cheng Su ◽

Zhaohui Feng ◽

William Rom ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Coal Workers Pneumoconiosis ◽

Coal Workers

Download Full-text

Transcriptome sequencing reveals e-cigarette vapor and mainstream-smoke from tobacco cigarettes activate different gene expression profiles in human bronchial epithelial cells

Scientific Reports ◽

10.1038/srep23984 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 40

Author(s):

Yifei Shen ◽

Michael J. Wolkowicz ◽

Tatyana Kotova ◽

Lonjiang Fan ◽

Michael P. Timko

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Transcriptome Sequencing ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Bronchial Epithelial Cells ◽

Mainstream Smoke ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial

Download Full-text

Azithromycin Increases Interferon and Interferon Stimulated Gene Expression and Has Anti-Rhinoviral Activity in Human Bronchial Epithelial Cells.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5158 ◽

2009 ◽

Author(s):

V Gielen ◽

SL Johnston ◽

MR Edwards

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial

Download Full-text

Bronchial epithelial compression regulates MAP kinase signaling and HB-EGF-like growth factor expression

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00270.2001 ◽

2002 ◽

Vol 282 (5) ◽

pp. L904-L911 ◽

Cited By ~ 69

Author(s):

Daniel J. Tschumperlin ◽

Jonathan D. Shively ◽

Melody A. Swartz ◽

Eric S. Silverman ◽

Kathleen J. Haley ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Epithelial Cells ◽

Compressive Stress ◽

Bronchial Epithelial Cells ◽

Heparin Binding ◽

Bronchial Epithelial ◽

Extracellular Signal ◽

Normal Human ◽

Kinase Phosphorylation

Airway smooth muscle constriction leads to the development of compressive stress on bronchial epithelial cells. Normal human bronchial epithelial cells exposed to an apical-to-basal transcellular pressure difference equivalent to the computed stress in the airway during bronchoconstriction demonstrate enhanced phosphorylation of extracellular signal-regulated kinase (ERK). The response is pressure dependent and rapid, with phosphorylation increasing 14-fold in 30 min, and selective, since p38 and c-Jun NH2-terminal kinase phosphorylation remains unchanged after pressure application. Transcellular pressure also elicits a ninefold increase in expression of mRNA encoding heparin-binding epidermal growth factor-like growth factor (HB-EGF) after 1 h, followed by prominent immunostaining for pro-HB-EGF after 6 h. Inhibition of the ERK pathway with PD-98059 results in a dose-dependent reduction in pressure-induced HB-EGF gene expression. The magnitude of the HB-EGF response to transcellular pressure and tumor necrosis factor (TNF)-α (1 ng/ml) is similar, and the combined mechanical and inflammatory stimulus is more effective than either stimulus alone. These results demonstrate that compressive stress is a selective and potent activator of signal transduction and gene expression in bronchial epithelial cells.

Download Full-text