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与帕金森病相关的差异表达基因和长链非编码RNA的鉴定

Identification of Differentially Expressed Genes and Long Noncoding RNAs Associated with Parkinson's Disease.

作者信息

Chi Lu-Mei, Wang Li-Ping, Jiao Dan

机构信息

Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

出版信息

Parkinsons Dis. 2019 Feb 5;2019:6078251. doi: 10.1155/2019/6078251. eCollection 2019.

Abstract

OBJECTIVES

This study aims to determine differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) associated with Parkinson's disease (PD) using a microarray.

METHODS

We downloaded the microarray data GSE6613 from the Gene Expression Omnibus, which included 105 samples. We selected 72 samples comprising 22 healthy control blood samples and 50 PD blood samples for further analysis. Later, we used Limma to screen DEGs and differentially expressed lncRNAs (DElncRNAs) and estimated their functions by the Gene Ontology (GO). Besides, the competing endogenous RNA (ceRNA) network, including microRNAs, lncRNAs, and mRNAs, was constructed to elucidate the regulatory mechanism. Furthermore, we performed the KEGG pathway enrichment with mRNAs in the ceRNA regulatory network and constructed a final network, including pathways, mRNAs, microRNAs, and lncRNAs.

RESULTS

Overall, we obtained 394 DEGs, including 207 upregulated DEGs and 187 downregulated DEGs, and 7 DElncRNAs, including 2 upregulated DElncRNAs and 5 downregulated DElncRNAs. Insulin-like growth factor-1 receptor (IGF1R) was considerably enriched in the endocytosis pathway. In the ceRNA regulation network, IGF1R was the target of hsa-miR-133b and lncRNAs of XIST, and PART1 could also be the target of hsa-miR-133b. While the upregulated DEGs were enriched in the GO terms of the cytoskeleton, cytoskeletal part, and microtubule cytoskeleton, the downregulated DEGs were enriched in the immune response. PRKACA was markedly enriched in numerous pathways, including the MAPK and insulin signaling pathways.

CONCLUSIONS

IGF1R, PRKACA, and lncRNA-XIST could be potentially involved in PD, and these diverse molecular mechanisms could support the development of the similar treatment for PD.

摘要

目的

本研究旨在通过微阵列确定与帕金森病(PD)相关的差异表达基因(DEG)和长链非编码RNA(lncRNA)。

方法

我们从基因表达综合数据库下载了微阵列数据GSE6613,其中包括105个样本。我们选择了72个样本,包括22个健康对照血液样本和50个PD血液样本进行进一步分析。随后,我们使用Limma筛选DEG和差异表达lncRNA(DElncRNA),并通过基因本体论(GO)评估它们的功能。此外,构建了包括微小RNA、lncRNA和mRNA的竞争性内源RNA(ceRNA)网络,以阐明调控机制。此外,我们对ceRNA调控网络中的mRNA进行KEGG通路富集,并构建了一个最终网络,包括通路、mRNA、微小RNA和lncRNA。

结果

总体而言,我们获得了394个DEG,包括207个上调的DEG和187个下调的DEG,以及7个DElncRNA,包括2个上调的DElncRNA和5个下调的DElncRNA。胰岛素样生长因子1受体(IGF1R)在内吞作用通路中显著富集。在ceRNA调控网络中,IGF1R是hsa-miR-133b和XIST的lncRNA的靶点,PART1也可能是hsa-miR-133b的靶点。上调的DEG在细胞骨架、细胞骨架部分和微管细胞骨架的GO术语中富集,而下调的DEG在免疫反应中富集。PRKACA在许多通路中显著富集,包括MAPK和胰岛素信号通路。

结论

IGF1R、PRKACA和lncRNA-XIST可能与PD相关,这些多样的分子机制可能支持PD类似治疗方法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/946b/6379850/f7b134cb4436/PD2019-6078251.001.jpg

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