Comprehensive expression profiles and bioinformatics analysis reveal special circular RNA expression and potential predictability in the peripheral blood of humans with idiopathic membranous nephropathy.

Abstract

The etiology of idiopathic membranous nephropathy (IMN) is considered to be closely associated with immunoregulation and genetic factors. Circular RNAs (circRNAs) have been found to regulate gene expression in various organisms, and to play an important role in multiple physiological and pathological processes, which may be involved in the pathogenesis of IMN. The purpose of the present study was to investigate the potential relationship between circRNAs in peripheral blood and disease. The diagnoses of IMN were confirmed using electron microscopy and immunofluorescence. Total RNA was isolated and microarray analysis was used to detect the expression levels of circRNAs in the peripheral blood of patients with IMN and in normal subjects. Selected genes from the microarray were selected and verified by reverse transcription-quantitative (RT-q)PCR. Bioinformatics tools were applied for further functional evaluation, and the potential disease predictability of circRNAs was determined using receiver-operating characteristic (ROC) curves. The results showed that a total of 955 differentially expressed circRNAs were found in blood samples, 645 of which were upregulated and 310 which were downregulated. In total, five candidate circRNAs were validated using RT-qPCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified numerous types of target genes and their corresponding microRNAs (miRNAs). The miRNAs identified were involved in biological processes and enriched in multiple important pathways, including the mitogen-activated protein kinase, transforming growth factor-β and Ras signaling pathways. The levels of circ_101319 were significantly higher (P<0.001) and exhibited promising diagnostic value in patients with IMN (area under ROC =0.89). The co-expression network constructed for circ_101319 indicated that it may be associated with membranous nephropathy-related pathways by mediating miRNAs. In conclusion, the present study revealed the expression and functional profile of differentially expressed circRNAs in the peripheral blood of patients with IMN, and provided new perspectives to predict and elucidate the development of IMN.