Asthma is a common health issue which poses an economic and social burden on patients. However, the pathogenesis of this disease remains poorly understood. Recent studies have highlighted the potential roles of lncRNA in the pathogenesis of asthma. Lin reported that the lncRNA TUG1 promoted airway smooth muscle cell proliferation and migration, contributing to asthma . The lncRNA ANRIL/miR-125a axis may be related to inflammation, exacerbation, and the severity of bronchial asthma . In this study, 884 upregulated and 513 downregulated lncRNAs were identified between 10 patients with asthma and 10 healthy controls; these factors may serve as biomarkers for bronchial asthma.
GO and KEGG pathway analyses were performed to identify enriched biological functions. According to the results of the GO analysis, DEGs were involved in processes such as cell-cell adhesion, neutrophil degranulation, cellular response to DNA damage stimuli, positive regulation of chemokine production. Previous studies demonstrated that these are important biological processes in asthma. Dysregulation of cell-cell adhesion leads to epithelial barrier destruction, which may facilitate penetration of environmental allergens, thereby activating the innate immune responses and increasing asthma severity and susceptibility . Airway neutrophilia is associated with asthma severity and is refractory to treatment with corticosteroids. Neutrophils can kill pathogens but may also damage the airways by affecting proteases and reactive oxygen species . Airway inflammation, oxidative damage, DNA damage, and repair protein levels in asthma have been found to be increased . Asthma is known as a chronic inflammatory disease, and processes related to chemokine production, MAPK activation, and NF-κB activation were detected in this study.
KEGG pathway analysis revealed that the differentially expressed mRNAs are mainly related to apoptosis and TLR, RIG-I-like receptor, NOD-like receptor, FOXO, and T helper 17 signaling pathway. Some of these pathways have been demonstrated crucial to the onset of asthma. For example, CD9 + B cells induce effector T cell cycle arrest in sub G0/G1 and apoptosis in asthmatic mice . RIG-I has long been known to serve as a pattern recognition receptor for viral detection. However, this receptor was also found to serve several functions as an RNA-responsiveness protein for various cellular activities, including cell development and proliferation . However, the role of RIG-I in asthma requires further study. TLRs recognize microbial, endogenous molecules, and environmental allergens and play an immune-modulatory role in asthma development . Bacterial infection-mediated activation of NOD-like receptors triggers allergic asthma by activating eosinophils, which interact with bronchial epithelial cells in the airway . FOXO has multiple biological functions, such as modulation of embryonic endothelial stem cell survival , regulation of ischemic brain injury , and vascular disease , which is a newly investigated aspect of asthma. In this study, we identified some classical biological processes and new processes in asthma, providing a foundation for further study.
We constructed a global signal transduction network to identify core genes with crucial roles in the pathogenesis of asthma. The mRNAs NFKB1, PRKACB, PIK3CA, PLCB1, and PLCG1 had the top five degrees in the gene signal network. NFKB1 is the NF-κB p105 subunit, a typical inflammation pathway gene, and is associated with asthma. The protein kinase cAMP-dependent catalytic subunit β (PRKACB) is a member of the serine/threonine protein kinase family. PRKACB plays a key role in apoptosis and cell differentiation and proliferation . The phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene encodes the PI3K-p110α protein, which activates the PI3K pathway and leads to dysregulated cell proliferation . PLCB1 encodes the protein phospholipase C β1 and plays an important role in intracellular transduction of many extracellular signals . The main function of PLCG1 is to encode phospholipase C γ1, which mainly catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate second messenger molecules . Most of these genes have not been sufficiently studied in asthma and require further investigation. However, some mRNAs showing high degrees were not correlated with lncRNAs.
LncRNAs exert their functions by modulating mRNA processing and post-transcriptional regulation. Based on the lncRNA–mRNA co-expression network, gene signal network, and FC in the based expression list, we identified the following lncRNAs: AC019050.1, MTCYBP3, KB-67B5.12, NONHSAT122646, HNRNPA1P12, and their related mRNAs (FOXO3, JUN, PIK3CA, CXCL8, and G0S2). FOXO is a subfamily of forkhead transcription factors and plays key roles in regulating many pathways that regulate processes such as apoptosis, insulin signaling, DNA repair, oxidative stress resistance, and longevity [27, 28]. As the core component of the AP-1 transcription factor complex, JUN is an important factor in cell survival, cell proliferation, and movement . According to previous studies, c-Jun can be a therapeutic target for cancer, vascular remodeling, acute inflammation, and rheumatoid arthritis . There is no clear conclusion regarding the functions of G0S2 in asthma. G0S2 is highly expressed in the liver, heart, and skeletal muscle [31, 32] and is expressed at low levels in some tumors . The roles of these lncRNAs and related mRNAs in asthma require further analysis.
Our study had some limitations. First, the patients were assessed during a stable period of asthma, and some patients took medications, which may have altered their gene expression. Second, the functions of the differentially expressed mRNAs and lncRNAs were based on bioinformatics analysis, and therefore must be verified in animal experiments. Finally, there may be differences in the composition of PBMCs between the healthy control and asthma groups which may lead to the detection of different genes. If single-cell sequencing technology can be used to detect gene expression in different components of cells, the results may be more accurate; this will be the focus of our future study.
In conclusion, using microarray analysis, we identified the core mRNAs and their related lncRNAs, as well as predicted the possible altered biological processes and signaling pathways. This study provides insight into the investigated targets of asthma, which may be useful as lncRNA-mediated therapy for asthma.