[帕金森病患者血浆长链非编码RNA表达谱和lnc-CTSD-5:1在PD细胞模型中的作用:一项基于ceRNA微阵列的研究]。

Z Ren, P Zhou, J Tian
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Competitive endogenous RNA (ceRNA) networks were also constructed using the differential lncRNAs with mRNAs and known microRNAs. Using MPP<sup>+</sup>-treated SHSY5Y cells as a PD cell model, the expressions of the key lncRNAs and their functions were examined.</p><p><strong>Results: </strong>We identified 316 genes and 986 lncRNAs showing significant differential expressions in PD patients (<i>P</i>< 0.05). The differentially expressed mRNAs and the potential cis-regulatable target genes of these lncRNAs were functionally annotated using GO and KEGG enrichment analysis, and the targeting relationship of the differentially expressed mRNAs and lncRNAs with microRNAs were predicted. Analysis of the ceRNA networks constructed based on the differentially expressed lncRNAs suggested that lncMTG2-1:1, lnc-CTSD-5:1, lnc-PCCA-3:1, lnc-VTCN1-3:1, lnc-ZNF25-7:1, and lnc-DAZ3-1:1 might be the key lncRNAs in PD. 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引用次数: 0

摘要

目的:探讨与帕金森病(PD)相关的关键基因和长链非编码rna (lncRNAs)。方法:采集6例PD患者和6例健康人外周血血浆标本。采用ceRNA微阵列技术检测mRNA和lncRNA表达谱,采用生物信息学方法分析差异表达基因。在差异表达lncRNAs的上游或下游10 kb范围内转录的差异表达mrna被定义为lncRNAs的潜在顺式可调节(Cis)靶基因。构建pd特异性蛋白-蛋白相互作用网络(PPI)。竞争性内源性RNA (ceRNA)网络也使用不同的lncrna与mrna和已知的microrna构建。以MPP+处理的SHSY5Y细胞为PD细胞模型,检测关键lncrna的表达及其功能。结果:共鉴定出316个基因和986个lncrna在PD患者中有显著差异表达(P< 0.05)。利用GO和KEGG富集分析对这些lncRNAs的差异表达mrna和潜在的顺式可调控靶基因进行功能标注,并预测差异表达mrna和lncRNAs与microRNAs的靶向关系。基于差异表达lncrna构建的ceRNA网络分析表明,lncMTG2-1:1、lnc-CTSD-5:1、lnc-PCCA-3:1、lnc-VTCN1-3:1、lnc-ZNF25-7:1和lnc-DAZ3-1:1可能是PD的关键lncrna。在MPP+处理的SH-SY5Y细胞中,lnc-CTSD-5:1的表达变化最为显著,沉默lnc-CTSD-5:1可明显恢复酪氨酸羟化酶的表达水平。结论:PD患者血浆lncRNA表达谱发生显著变化,本研究发现的差异表达基因和lncRNA可能为探索PD发病机制和鉴定PD潜在生物标志物提供新的线索。
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[Plasma long noncoding RNA expression profiles in patients with Parkinson's disease and the role of lnc-CTSD-5:1 in a PD cell model: a ceRNA microarray-based study].

Objective: To explore the key genes and long non-coding RNAs (lncRNAs) associated with Parkinson's disease (PD).

Methods: Peripheral blood plasma samples were collected from 6 PD patients and 6 healthy individuals. The mRNA and lncRNA expression profiles were detected using ceRNA microarray technology, and the differentially expressed genes were analyzed using bioinformatics methods. The differentially expressed mRNAs transcribed within 10 kb upstream or downstream of the differentially expressed lncRNAs were defined as potential cis-regulatable (Cis) target genes of the lncRNAs. A PD-specific protein-protein interaction network (PPI) was constructed. Competitive endogenous RNA (ceRNA) networks were also constructed using the differential lncRNAs with mRNAs and known microRNAs. Using MPP+-treated SHSY5Y cells as a PD cell model, the expressions of the key lncRNAs and their functions were examined.

Results: We identified 316 genes and 986 lncRNAs showing significant differential expressions in PD patients (P< 0.05). The differentially expressed mRNAs and the potential cis-regulatable target genes of these lncRNAs were functionally annotated using GO and KEGG enrichment analysis, and the targeting relationship of the differentially expressed mRNAs and lncRNAs with microRNAs were predicted. Analysis of the ceRNA networks constructed based on the differentially expressed lncRNAs suggested that lncMTG2-1:1, lnc-CTSD-5:1, lnc-PCCA-3:1, lnc-VTCN1-3:1, lnc-ZNF25-7:1, and lnc-DAZ3-1:1 might be the key lncRNAs in PD. In MPP+-treated SH-SY5Y cells, the expression of lnc-CTSD-5:1 showed the most significant changes, and silencing lnc-CTSD-5:1 obviously restored the expression level of tyrosine hydroxylase.

Conclusion: PD patients have significant changes in plasma lncRNA expression profile, and the differentially expressed genes and lncRNAs found in this study may provide new clues for exploring the pathogenesis and identifying potential biomarkers of PD.

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南方医科大学学报杂志
南方医科大学学报杂志 Medicine-Medicine (all)
CiteScore
1.50
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0.00%
发文量
208
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