Abstract：
BACKGROUND: Eukaryotic elongation factor 1A1 (eEF1A1) is an RNA-binding protein that is associated with PARK2 activity in cells, suggesting a possible role in Parkinson\'s disease (PD).
OBJECTIVE: To clear whether eEF1A1 plays a role in PD through transcriptional or posttranscriptional regulation.
METHODS: The GSE68719 dataset was downloaded from the GEO database, and the RNA-seq data of all brain tissue autopsies were obtained from 29 PD patients and 44 neurologically normal control subjects. To inhibit eEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells, and RNA-seq high-throughput sequencing was used to determine the differentially expressed genes (DEGs) and differentially alternative splicing events (ASEs) resulting from eEF1A1 knockdown.
RESULTS: eEF1A1 was significantly overexpressed in PD brain tissue in the BA9 area. GO and KEGG enrichment analyses revealed that eEF1A1 knockdown significantly upregulated the expression of the genes CXCL10, NGF, PTX3, IL6, ST6GALNAC3, NUPR1, TNFRSF21, and CXCL2 and upregulated the alternative splicing of the genes ACOT7, DDX10, SHMT2, MYEF2, and NDUFAF5. These genes were enriched in pathways related to PD pathogenesis, such as apoptosis, inflammatory response, and mitochondrial dysfunction.
CONCLUSIONS: The results suggesting that eEF1A1 involved in the development of PD by regulating the differential expression and alternative splicing of genes, providing a theoretical basis for subsequent research.
OBJECTIVE: To clear whether eEF1A1 plays a role in PD through transcriptional or posttranscriptional regulation.
METHODS: The GSE68719 dataset was downloaded from the GEO database, and the RNA-seq data of all brain tissue autopsies were obtained from 29 PD patients and 44 neurologically normal control subjects. To inhibit eEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells, and RNA-seq high-throughput sequencing was used to determine the differentially expressed genes (DEGs) and differentially alternative splicing events (ASEs) resulting from eEF1A1 knockdown.
RESULTS: eEF1A1 was significantly overexpressed in PD brain tissue in the BA9 area. GO and KEGG enrichment analyses revealed that eEF1A1 knockdown significantly upregulated the expression of the genes CXCL10, NGF, PTX3, IL6, ST6GALNAC3, NUPR1, TNFRSF21, and CXCL2 and upregulated the alternative splicing of the genes ACOT7, DDX10, SHMT2, MYEF2, and NDUFAF5. These genes were enriched in pathways related to PD pathogenesis, such as apoptosis, inflammatory response, and mitochondrial dysfunction.
CONCLUSIONS: The results suggesting that eEF1A1 involved in the development of PD by regulating the differential expression and alternative splicing of genes, providing a theoretical basis for subsequent research.
摘要：
背景：真核延伸因子1A1（eEF1A1）是一种与细胞中PARK2活性相关的RNA结合蛋白，提示在帕金森病（PD）中的可能作用。
目的：明确eEF1A1是否通过转录或转录后调控在PD中发挥作用。
方法：从GEO数据库下载GSE68719数据集，所有脑组织尸检的RNA-seq数据来自29例PD患者和44例神经系统正常对照受试者。为了抑制eEF1A1在U251细胞中的表达，siRNA被转染到这些细胞中，和RNA-seq高通量测序用于确定由eEF1A1敲低产生的差异表达基因(DEGs)和差异可变剪接事件(ASEs)。
结果：eEF1A1在BA9区PD脑组织中显著过表达。GO和KEGG富集分析显示eEF1A1敲低显著上调CXCL10、NGF、PTX3、IL6、ST6GALNAC3、NUPR1、TNFRSF21和CXCL2并上调ACOT7、DDX10、SHMT2、MYEF2和NDUFAF5基因的可变剪接。这些基因富含与PD发病机制相关的通路，如细胞凋亡，炎症反应，和线粒体功能障碍。
结论：结果表明，eEF1A1通过调节基因的差异表达和可变剪接参与PD的发生，为后续研究提供理论基础。
目的：明确eEF1A1是否通过转录或转录后调控在PD中发挥作用。
方法：从GEO数据库下载GSE68719数据集，所有脑组织尸检的RNA-seq数据来自29例PD患者和44例神经系统正常对照受试者。为了抑制eEF1A1在U251细胞中的表达，siRNA被转染到这些细胞中，和RNA-seq高通量测序用于确定由eEF1A1敲低产生的差异表达基因(DEGs)和差异可变剪接事件(ASEs)。
结果：eEF1A1在BA9区PD脑组织中显著过表达。GO和KEGG富集分析显示eEF1A1敲低显著上调CXCL10、NGF、PTX3、IL6、ST6GALNAC3、NUPR1、TNFRSF21和CXCL2并上调ACOT7、DDX10、SHMT2、MYEF2和NDUFAF5基因的可变剪接。这些基因富含与PD发病机制相关的通路，如细胞凋亡，炎症反应，和线粒体功能障碍。
结论：结果表明，eEF1A1通过调节基因的差异表达和可变剪接参与PD的发生，为后续研究提供理论基础。
