Expression signatures of long non-coding RNA in the substantia nigra of pre-symptomatic mouse model of Parkinson's disease
Expression signatures of long non-coding RNA in the substantia nigra of pre-symptomatic mouse model of Parkinson's disease
复制标题
帕金森病症状前小鼠模型黑质中长非编码RNA的表达特征
DOI：
10.1016/j.bbr.2017.04.044
复制
发表时间：
2017-07-28
影响因子：
2.7
通讯作者：
Tian, Bo
中科院分区：
文献类型：
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作者：
Jiao, Fengjuan;Wang, Qingzhi;Tian, Bo
帕金森病（PD）是一种年龄依赖性神经退行性疾病，可由多种因素引起。越来越多的证据表明，PD运动相前可表达分子或影像学标志物。许多长链非编码RNA（lncRNA）已在神经退行性疾病中被鉴定。然而，lncRNA在PD症状前阶段的生物起源和功能知之甚少。在此，我们通过微阵列分析分析了过度表达人A30 P * A53 T α-突触核蛋白的症状前小鼠黑质致密部（SNpc）中lncRNA和mRNA的表达。基于Pearson相关分析，构建了1ncRNA/mRNA共表达网络。对lncRNA共表达的mRNA进行GO富集和通路分析，以确定相关的生物学功能和病理通路。实时荧光定量PCR检测lncRNA的表达模式。在早期过表达人A30 P * A53 T α-突触核蛋白转基因小鼠的SNpc中，约有756种IncRNA异常表达，包括477种下调的IncRNA和279种上调的IncRNA。GO分析表明，这些lncRNA共表达的mRNA靶向转录（本体：生物过程），膜（本体：细胞成分）和蛋白质结合（本体：分子功能）的调节。通路分析表明lncRNA共表达的mRNA主要富集在轴突导向信号通路中。总之，本研究首次发现了一系列由突变型α-突触核蛋白引起的新的早期PD相关IncRNA。进一步研究这些异常表达的IncRNA的功能可能为早期PD的治疗提供新的思路。
Parkinson's disease (PD) is an age-dependent neurodegenerative disease that can be caused by a variety of factors. Growing evidence shows that prior to the motor phase of PD can express molecular or imaging markers. Many long non-coding RNAs (lncRNAs) have been identified in neurodegenerative disease. However, the biogenesis and function of lncRNAs in the pre-symptomatic stage of PD is poorly understood. Here, we profiled the expression of lncRNAs and mRNAs in the substantia nigra pars compacts (SNpc) of pre-symptomatic mice over-expressing human A30P*A53T alpha-synuclein by microarray analysis. Based on the Pearson correlation analysis, 1ncRNA/mRNA co-expression network was constructed. GO enrichment and pathway analysis of lncRNAs-coexpressed mRNAs was conducted to identify the related biological function and pathologic pathways. Real-time PCR was used to detect the expression pattern of lncRNAs. Approximately 756 IncRNAs were aberrantly expressed in the SNpc of early over-expressing human A30P*A53T alpha-synuclein transgenic mice, including 477 downregulated lncRNAs and 279 upregulated lncRNAs. GO analysis indicated that these lncRNAs-coexpressed mRNAs were targeted to regulation of transcription (ontology: biological process), membrane (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis indicated that lncRNAs-coexpressed mRNAs were mostly enriched in axon guidance signaling pathway. In conclusion, the present study firstly identified a series of novel early PD-associated IncRNAs caused by mutant alpha-synuclein. Further study the function of these aberrantly expressed IncRNAs may provide insight into treatment of early PD.