MicroRNA-4639 Is a Regulator of DJ-1 Expression and a Potential Early Diagnostic Marker for Parkinson's Disease.
MicroRNA-4639 Is a Regulator of DJ-1 Expression and a Potential Early Diagnostic Marker for Parkinson's Disease.
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MicroRNA-4639 是 DJ-1 表达的调节剂，也是帕金森病的潜在早期诊断标志物
DOI：
10.3389/fnagi.2017.00232
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发表时间：
2017
影响因子：
4.8
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Chen Y;Gao C;Sun Q;Pan H;Huang P;Ding J;Chen S
帕金森病（PD）是第二大常见的神经退行性疾病，对患者的日常生活有着深远的影响。然而，目前缺乏有效的生物标志物进行早期诊断，PD的发病机制仍不清楚。microRNA（miRNAs）是一种转录后基因调控因子，在血浆中易于检测，具有良好的诊断价值。本研究旨在探索一种外周血生物标志物，不仅可用于PD的早期诊断，而且有可能成为治疗靶点。通过对169例散发性PD患者、170例健康对照和60例特发性震颤（ET）患者血浆中的miRNA微阵列筛选和进一步验证，确定了hsa-miR-4639- 5 p水平在PD患者中显著上调。此外，它能够区分早期PD患者（病程≤2年或Hoehn和Yahr 1-2.5期）和健康对照。此外，hsa-miR-4639- 5 p显示在转录后水平负调控PD相关基因DJ-1（PARK 7）。hsa-miR-4639- 5 p的异常上调导致DJ-1蛋白水平下调，导致严重的氧化应激和神经元死亡。总之，hsa-miR-4639- 5 p有可能成为早期PD的外周诊断生物标志物和治疗靶点。
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and has profound impacts on the daily lives of patients. However, there is a lack of effective biomarkers for early diagnosis, and the mechanisms of PD pathogenesis remain obscure. microRNAs (miRNAs) are post-transcriptional gene regulators and can be easily detected in plasma, which suggests a promising role as diagnostic markers. Here, we aimed to explore a peripheral biomarker, which not only can be applied for early diagnosis of PD but also has the potential to be a therapeutic target. Through miRNA microarray screening and further validation in plasma from 169 sporadic PD patients, 170 healthy controls, and 60 essential tremor (ET) patients, hsa-miR-4639-5p level was identified to be significantly up-regulated in PD patients. Also, it was able to discriminate between early PD patients (disease duration ≤2 years or Hoehn and Yahr stage 1–2.5) and healthy controls. Furthermore, hsa-miR-4639-5p was shown to negatively regulate DJ-1 (PARK7), a well-known PD-related gene, in the post-transcriptional level. Abnormal up-regulation of hsa-miR-4639-5p caused down-regulation of DJ-1 protein level, leading to severe oxidative stress and neuronal death. In conclusion, hsa-miR-4639-5p has the potential to be a peripheral diagnostic biomarker and therapeutic target for early PD.
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