MicroRNA-409-3p Targeting at ATXN3 Reduces the Apoptosis of Dopamine Neurons Based on the Profile of miRNAs in the Cerebrospinal Fluid of Early Parkinson's Disease.
MicroRNA-409-3p Targeting at ATXN3 Reduces the Apoptosis of Dopamine Neurons Based on the Profile of miRNAs in the Cerebrospinal Fluid of Early Parkinson's Disease.
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DOI：
10.3389/fcell.2021.755254
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发表时间：
2021
影响因子：
5.5
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Tan X;Hu J;Ming F;Lv L;Yan W;Peng X;Bai R;Xiao Q;Zhang H;Tang B;Wang C;Tan J
早期帕金森病（PD）的精确识别一直是一项具有挑战性的任务，需要整合更多可行的生物标志物以提高诊断准确性。脑脊液（CSF）中的microRNAs（miRNAs）被认为是PD潜在的和有希望的候选生物标志物。然而，CSF中改变的miRNA在PD中的作用尚不清楚。在这里，我们招募了早期PD患者和对照组，通过下一代测序（NGS）分析CSF中miRNA的表达。此外，我们使用实时定量PCR检测了MPP+处理的SH-SY 5 Y细胞中这些miRNA的水平。我们发现21个miRNAs在早期PD患者的CSF中上调，并且miR-409- 3 p（所鉴定的21个miRNAs之一）在MPP+处理的SH-SY 5 Y细胞中得到进一步证实。此外，当SH-SY 5 Y细胞和小鼠分别用MPP+和MPTP处理时，更多的细胞在miR-409- 3 p过表达组中存活。在机制上，我们通过双荧光素酶报告基因测定证明了miR-409- 3 p和ATXN 3的3 'UTR的结合。此外，miR-409- 3 p模拟物减少了ATXN 3的聚谷氨酰胺扩增突变体的聚集和凋亡。我们的研究结果为CSF中的miR-409- 3 p作为PD的诊断标志物提供了实验证据。
Precise recognition of early Parkinson’s disease (PD) has always been a challenging task requiring more feasible biomarkers to be integrated to improve diagnostic accuracy. MicroRNAs (miRNAs) of cerebrospinal fluid (CSF) are believed to be potential and promising candidate biomarkers for PD. However, the role of altered miRNAs of CSF play in PD is unclear. Here, we recruited patients with early stages of PD and controls to analyze the expression of miRNA in CSF by the Next Generation Sequencing (NGS). Furthermore, we tested the levels of these miRNA in SH-SY5Y cells treated with MPP+ using real-time quantitative PCR. We found 21 miRNAs were upregulated in CSF of early PD patients and miR-409-3p, one of the identified 21 miRNAs, was further confirmed in SH-SY5Y cells treated with MPP+. Also, more cells survived in the overexpression of the miR-409-3p group when SH-SY5Y cells and mice were treated with MPP+ and MPTP, respectively. Mechanistically, we demonstrated the binding of miR-409-3p and 3’UTR of ATXN3 through a dual luciferase reporter gene assay. Moreover, miR-409-3p mimic reduced the aggregation of polyglutamine-expanded mutant of ATXN3 and apoptosis. Our results provide experimental evidence for miR-409-3p in CSF as a diagnostic marker of PD.
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影响因子：
4.3
作者：
Roser AE;Caldi Gomes L;Schünemann J;Maass F;Lingor P
通讯作者：
Lingor P
影响因子：
5.1
作者：
Marques TM;Kuiperij HB;Bruinsma IB;van Rumund A;Aerts MB;Esselink RAJ;Bloem BR;Verbeek MM
通讯作者：
Verbeek MM
DOI：
10.1136/jnnp-2013-307539
发表时间：
2014-10
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Magdalinou N;Lees AJ;Zetterberg H
通讯作者：
Zetterberg H
影响因子：
6.1
作者：
Pozzi, Chiara;Valtorta, Marco;Fusi, Paola
通讯作者：
Fusi, Paola
帕金森病患者脑脊液hsa-miR-626变化的初步研究
影响因子：
2
作者：
Qin, Li-xia;Tan, Jie-qiong;Wang, Chun-yu
通讯作者：
Wang, Chun-yu