Department of Neurology, Ludwig Maximilian University, Munich, Germany; Department of Translational Neurodegeneration, German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany.
Technical University of Munich Medical School, Munich, Germany; Department of Translational Neurodegeneration, German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany.
Parkinsonism Relat Disord. 2021 Jul;88:46-50. doi: 10.1016/j.parkreldis.2021.05.022. Epub 2021 Jun 1.
In 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.
Patients 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.
Statistical 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).
Our 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.
在本研究中，我们旨在研究特发性帕金森病（PD）患者常规结肠活检中 microRNAs（miRNAs）的表达，并探讨其作为 PD 诊断生物标志物的价值及其对 PD 发病和进展的机制贡献。
前瞻性招募 PD 患者（n=13）和健康对照者（n=17）进行常规结肠活检以进行癌症筛查。从活检材料中提取总 RNA，并通过 Illumina 高通量测序定量测定 miRNAs 的表达。
统计分析显示，与对照组相比，PD 患者的结肠活检组织中黏膜下 hsa-miR-486-5p 明显富集。miR-486-5p 的表达与年龄和 UPDRS 及 Hoehn & Yahr 量表测量的疾病严重程度相关。miRNA 基因靶标分析确定了受 miR-486-5p 影响的 301 个基因靶标。随后的关联靶标鉴定和通路富集分析进一步确定了它们在肠神经系统（ENS）中不同生物学过程中的作用。
我们的研究表明，PD 患者的常规结肠活检组织中存在黏膜下 miR-486-5p 的富集。我们的研究结果将支持将 miR-486-5p 作为 PD 生物标志物进行研究，并有助于理解 miR-486-5p 基因靶标对 PD 发病和进展的意义。此外，我们的数据将支持对 PD 中胃肠道功能障碍的分子和细胞机制的研究。
