Dysregulation of human miRNAs and increased prevalence of HHV miRNAs in obese periodontitis subjects.

Abstract

To evaluate human and herpesvirus-encoded microRNA (miRNA) expression in healthy and diseased gingiva of obese and non-obese subjects and compare the impact of localized and systemic inflammation on human miRNA profiles. Healthy and inflamed gingival biopsies were collected from obese and non-obese subjects. Human and herpesvirus miRNA expression was quantified using quantitative PCR. Predicted targets of dysregulated miRNAs were identified using bioinformatics analysis, validated by dual luciferase assays and their expression assessed in healthy and diseased tissues. Our results show differential expression of miRNAs in both diseased groups compared to healthy counterparts. MMP-16 is identified as a novel target of miRNAs altered in disease. Expression analysis of genes predicted as target of differentially expressed miRNAs show significant changes in disease compared with healthy tissues. Finally, quantitation of four herpesvirus-derived viral miRNAs show that the expression and prevalence of herpesvirus miRNAs in diseased gingiva of obese subjects. Our findings show that miRNA (both cellular and virus) expression is differentially responsive to local and systemic inflammation. Some of these miRNAs can modulate key cellular genes with direct consequences on inflammatory pathways suggesting their impact on oral tissue transcriptome and functions.