Circulating miR-218-5p is downregulated in the extracellular vesicles of patients with psoriatic arthritis

Abstract

Abstract Background There is an urgent need to identify biomarkers for psoriatic arthritis to assist with early diagnosis. MicroRNAs (miRNAs) play a pivotal role in psoriatic arthritis. To investigate the difference between plasma extracellular vesicle (EV) miRNA profiles of psoriasis patients without psoriatic arthritis (PsO) and patients with psoriasis and psoriatic arthritis (PsA). Methods Plasma EV isolation and next-generation sequencing were performed to identify differentially expressed EV miRNAs between patients with PsO (n = 15) and those with PsA (n = 8). miRNA target genes were predicted via miRNA target-predicting tools (TargetScan, miRDB, MIRDIP) and further validated by western blotting. GO and KEGG enrichment analyses were performed on these target genes. Additionally, a receiver operating characteristic (ROC) analysis was performed to assess the diagnostic value of the selected miRNA candidates. Results Among a complete profile of 597 miRNAs detected, 15 miRNAs were significantly altered in PsA, including two upregulated miRNAs and 13 downregulated miRNAs. According to the results from miRNA target-predicting tools and our previous quantitative iTRAQ-based proteomics study, miR-218-5p and its possible target ADP-ribosylation factor 6 (ARF6) provoked our interest. The higher expression of ARF6 in PsA was validated via western blotting in validation samples, and ROC curve analysis further revealed that miR-218-5p was a diagnostic candidate (AUC = 0.758; P value = 0.023). GO and KEGG pathway analyses were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway and epithelial cell apoptotic process. Conclusions This pilot study revealed that miR-218-5p is downregulated in the EVs of patients with PsA and could serve as a candidate biomarker to distinguish PsA from PsO, which may be a strategy for PsA diagnosis.