Differential expression of gut miRNAs in idiopathic Parkinson's disease

Abstract

ObjectiveIn the present work, we aimed to investigate the expression of microRNAs (miRNAs) in routine colonic biopsies obtained from patients with idiopathic Parkinson's disease (PD) and to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression. MethodsPatients with PD (n = 13) and healthy controls (n = 17) were prospectively recruited to undergo routine colonic biopsies for cancer screening. Total RNA was extracted from the biopsy material and the expression of miRNAs was quantified by Illumina High-Throughput Sequencing. ResultsStatistical analysis revealed a significant submucosal enrichment of the miRNA hsa-miR-486–5p in colonic biopsies from PD patients compared to the control subjects. The expression of miR-486–5p correlated with age and disease severity as measured by the UPDRS and Hoehn & Yahr scale. miRNA gene target analysis identified 301 gene targets that are affected by miR-486–5p. A follow-up associated target identification and pathway enrichment analysis further determined their role in distinct biological processes in the enteric nervous system (ENS). InterpretationOur work demonstrates an enrichment of submucosal miR-486–5p in routine colonic biopsies from PD patients. Our results will support the examination of miR-486–5p as a PD biomarker and help to understand the significance of the miR-486–5p gene targets for PD onset and progression. In addition, our data will support the investigation of the molecular and cellular mechanisms of GI dysfunction in PD.