For a study, researchers sought to find dysregulated microRNAs (miRNAs) from urine small Extracellular Vesicles (sEVs) and investigate their possible involvement in nephrolithiasis.

Participants’ initial morning voids were taken. Ultracentrifugation and sequential differential centrifugation were used to isolate urinary exosomes. Three calcium oxalate (CaOx) stone patients and three age- and sex-matched healthy controls’ urine sEV transcriptomes were examined using next-generation sequencing. The relationship between dysregulated miRNAs and stone formation was investigated using bioinformatics analysis. They identified 3 similar miRNAs after comparing the dysregulated miRNAs from the investigation with the miRNA sequencing data of sEVs produced from epithelial cells (GSE110509).

There were 54 dysregulated miRNAs between the control and stone groups, of which 14 were down-regulated, and 40 were up-regulated in the stone groups in comparison to the control groups. Focal adhesion (a cellular component), oxidative stress (a biological process), and cell adhesion molecule binding  (Molecular Function) were all shown to be enriched in dysregulated miRNAs indicated by gene ontology (GO) analysis. Analysis of the pathways included in the Kyoto Encyclopedia of Genes and Genomes revealed that dysregulated miRNAs were frequently abundant in the focal adhesion, MAPK signaling pathway, and AGE-RAGE signaling pathways. Both the sEVs obtained from cells (GSE110509) and the sEVs derived from urine considerably differed in the expression of miR-223-3p, miR-127-3p, and miR-214-5p. QPCR verified that urine sEVs isolated from CaOx stone patients expressed more miR-223-3p.

MiR-223-3p may influence stone formation by modulating oxidative stress, focal adhesion, and inflammatory processes since its expression is much greater in urinary sEVs obtained from CaOx stone patients.