Transcriptome analysis of human peripheral blood reveals key circRNAs implicated in Allergic bronchopulmonary aspergillosis

摘要

Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease characterized by aspergillus induced allergic inflammation. ABPA is one of most widespread disease in the world, up to now, there are more than 5 million ABAP patients all over the world. In the western countries, ABPA usually can be seen in bronchial asthma and cystic fibrothersis patients, and it can be found in asthma and bronchiectasia patients in China. Currently, a well-accepted theoretical basis for ABPA is Aspergillus spores is drawn in via the mouth and nose and grow into Aspergillus hypha in the surface of airway epithelial cells, and release proteolytic enzyme and other toxic substances, which will destroy airway epithelium and activate epithelial cell. Activated epithelial cell further release a series of pro-inflammatory cytokines and B-lymphocyte chemoattractant to promote inflammatory response. In the meanwhile, the airway epithelium destroyed by proteolytic enzyme will enhance the transport and delivery of aspergillus antigens and other allergens, which will induce Th2-type immune response and produce IL-4, IL-5 and IL-13. IL-4 and IL-3 will induce B cell to produce IgE and activate mastocyte, and IL-5 will lead to the degranulation of oxyphil cells. Finally, the specific IgE mediated type I allergic reactions will lead to damage in the airway wall and surrounding tissue. The clinical manifestations are asthma and expectoration. Still, the pathogenesis of ABPA is still unclear so far. Some studies demonstrated that the pathogenesis of ABPA is correlated to the genetic type of host. For example, some researchers found that there are some mutations and SNPs existed in immune-related genes of ABPA patients via whole genome sequence analysis. In addition, some studies showed that ABPA is associated to HLA-DR2 and HLA-DR5 genes. However, most studies focus on coding sequences, few refer to non-coding level. Circular RNAs (circRNAs) are currently regarded as crucial RNAs involved in diverse biological process and pathways and correlated to many diseases. CircRNAs are generated from the backsplicing of exon, introns or both to form exonic or intronic circRNAs. It has been proposed that circRNAs regulate gene expression at transcriptional or post-transcriptional level by interacting with microRNAs and act as microRNAs sponges for microRNAs. In addition, circRNAs have been found to be closely correlated to cancer and be more often downregulated in tumor tissue. So far, the potential roles of circRNAs in ABPA is still poorly understood. Thus, in the present study, with the aim at identifying potential circRNAs implicated in ABPA, we performed transcriptome analysis based on the deep RNA sequencing in eight human peripheral blood samples, in which five samples from ABPA patients and three from healthy people. The results showed that numerous circRNAs specifically expressed in the peripheral blood of ABPA patients. Furthermore, target microRNAs prediction of those differentially expressed circRNAs indicated that many microRNAs probably interacted with these circRNAs, implying complex regulations of these noncoding RNAs in response to ABPA.