Su Lining, Wang Chunjie, Zheng Chenqing, Wei Huiping, Song Xiaoqing
Department of Biology of Basic Medical Science College, Hebei North University, Zhangjiakou, 075000, Hebei, China.
Department of Basic Medicine, Zhangjiakou University, Zhangjiakou, 75000, Hebei, China.
BMC Med Genomics. 2018 Apr 13;11(1):40. doi: 10.1186/s12920-018-0357-7.
Parkinson's disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation.
We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network.
Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3'-untranslated region of genes and are controlled by several miRNAs.
Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD.
帕金森病（PD）是一种由环境和遗传因素引起的长期退行性疾病。控制PD进展和发展的基因及其调控因子网络需要进一步阐明。
我们通过荟萃分析检查了来自多个PD血液和黑质（SN）微阵列数据集的常见差异表达基因（DEG）。进一步使用GCBI从常见DEG中筛选出PD特异性基因。接下来，我们使用一系列生物信息学软件分析与常见PD特异性基因相关的miRNA、lncRNA和SNP，然后识别mTF-miRNA-基因-gTF网络。
我们的结果在PD血液研究中鉴定出36个常见DEG，在PD SN研究中鉴定出17个常见DEG，其中5个基因先前已知与PD相关。对与常见PD特异性基因相关的调控miRNA的进一步研究在我们的研究中揭示了14个PD特异性miRNA。对PD特异性基因的mTF-miRNA-基因-gTF网络分析揭示了两个前馈环：一个涉及SPRK2基因、hsa-miR-19a-3p和SPI1，另一个涉及SPRK2基因、hsa-miR-17-3p和SPI。长链非编码RNA（lncRNA）介导的调控网络鉴定出与PD特异性基因和PD特异性miRNA相关的lncRNA。此外，对PD特异性基因的单核苷酸多态性（SNP）分析鉴定出两个显著的SNP，对神经退行性疾病特异性基因的SNP分析鉴定出七个显著的SNP。这些SNP大多存在于基因的3'非翻译区，并受几种miRNA调控。
我们的研究在血液和脑数据集中将PD患者与健康对照相比共鉴定出53个常见DEG，其中5个基因先前与PD相关。调控网络分析鉴定出PD特异性miRNA、相关长链非编码RNA和前馈环，这有助于我们理解PD的潜在机制。我们研究中鉴定出的SNP可确定基因变异是否与PD相关。总体而言，这些发现将有助于指导我们对PD复杂分子机制的研究。
