Differential Expression Profile of miRNA in Urine Exosomes of Patients with Calcium Oxalate Stones and Its Bioinformatics Analysis.

Abstract

Background: Extracellular microRNA (miRNA) (exosomal miRNA) embedded in exosomes plays a vital role in the progression of calcium oxalate disease. This study aimed to identify dysregulated miRNA expression profiles and their biological functions in the urinary exosomes of patients with calcium oxalate.

Methods: Ultrahigh-speed centrifugation and Illumina high-throughput sequencing were used to isolate and detect the expression levels of exocrine miRNAs in urine samples from 10 patients with calcium oxalate stones and 10 matched normal persons, and construct their differential expression profiles. Bioinformatics analysis of differentially expressed genes was carried out to determine the main biological functions of differentially expressed miRNAs and their possible signal pathways.

Results: Compared with normal people, 38 miRNAs in the urinary exosomes of patients with calcium oxalate stones showed significantly abnormal expression levels, of which 18 were up-regulated and 20 were down-regulated. Gene Ontology (GO) enrichment analysis showed that the differentially expressed miRNAs were related to biological processes such as calcium transport, inflammation, injury, oxidative stress and adhesion. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differentially expressed miRNAs may participate in the occurrence and development of calcium oxalate stones through cytokines and inflammatory response-related signalling pathways such as chemokine signalling pathway, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signalling pathway, mitogen-activated protein kinases (MAPK) signalling pathway and Rat sarcoma (RAS) signalling pathway.

Conclusions: The expression profile of miRNA in the urine exosomes of patients with calcium oxalate stones changed significantly. miRNAs, such as miR-130b, miR-192, miR-194 and miR-499, may play important roles in the occurrence and development of calcium oxalate stones through cytokines and inflammatory response-related signal pathways, including chemokine, PI3K-AKT, MAPK and RAS.