Identification and comparison of novel circular RNAs with associated co-expression and competing endogenous RNA networks in pulmonary tuberculosis

Pulmonary tuberculosis (PTB) is caused by Mycobacterium tuberculosis and is one of the most serious diseases worldwide. Circular RNAs (circRNAs) are a large class of non-coding RNAs that were identified with potential regulatory roles in disease pathogenesis and progression. In this study, we used whole transcriptome sequencing to identify circRNAs from 3 PTB patients and 3 healthy individuals to determine the expression pattern of circRNAs in blood and the circRNA molecular regulatory networks in PTB pathogenesis. One hundred and seventy differentially expressed (≥ 2-fold change) circRNAs were dysregulated in PTB, compared with in healthy individuals. Quantitative real-time polymerase chain reaction was used to validate the RNA sequencing analysis from 20 PTB patients, and the results were consistent with the sequencing data. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis were applied to explore the potential circRNA functions of the significantly deregulated genes. Several immunity pathways, including endocytosis pathways in cancer, mitogen-activated protein kinase signaling pathway, human T-lymphotropic virus type 1 infection, and ubiquitin-mediated proteolysis, were involved in PTB pathogenesis. Competing endogenous RNAs (ceRNA) were constructed and inferred that aberrant expression of circRNA-associated ceRNA resulted in extensive variation in gene expression by miRNA-mediated circRNA-mRNA crosstalk interactions. Our study revealed that the circRNA–miRNA–mRNA network may shed light on the biological functions of circRNAs in PTB and provide useful information for exploring potential roles of circRNA in PTB.