G. Erre1, M. Piga2, C. Carru3, A. Angius4, L. Carcangiu5, M. Piras6, S. Sotgia7, A. Zinellu8, A. Mathieu9, G. Passiu10, M. Pescatori11
2015 Vol.33, N°6 ,Suppl.94 - PI 0072, PF 0079
To explore the post-transcriptional regulation of the peripheral blood mononuclear cells (PBMCs) transcriptome by microRNAs in Behçet’s disease (BD).
Using TaqMan Low Density Array-based microRNAs expression profiling, the expression of 750 mature human microRNAs in PBMCs from 5 BD patients and 3 healthy controls (HC) was compared. The expression of deregulated microRNAs was then validated by quantitative real time-poly-merase chain reaction (qRT-PCR), in 42 BD patients and 8 HC.
In the initial screening, 13 microRNAs appeared deregulated in BD vs HC. Among them, the differential expression of miR-720 and miR-139-3p was confirmed by qRT-PCR, (p<0.05 and FDR <5%). Areas under the receiver operating characteristic curve for miR-139-3p, miR-720 and miR-139-3p + miR-720 in the validation cohort were 0.84, 0.87 and 0.92 respectively, indicating good discrimination between BD patients and HC. Post-hoc analysis showed that 9 out of 13 microRNAs from the discovery phase were significantly upregulated in active vs. quiescent BD, suggesting inflammation as a key regulator of microRNAs machinery in BD. In silico analysis revealed that several BD candidate susceptibility genes are predicted target of significantly deregulated microRNAs in active BD. A significant enrichment in microRNAs targeting elements of the Toll-like receptor (TLR) and T-cell receptor signalling pathways was also assumed.
miR199-3p and miR720 deserve further confirmation as biomarkers of BD in larger studies. PBMCs from active BD displayed a unique signature of microRNAs which may be implicated in regulation of innate immunity activation and T-cell function.
PMID: 26486198 [PubMed]
Received: 25/10/2014 - Accepted : 27/05/2015 - In Press: 19/10/2015 - Published: 04/11/2015