EEF1A1 knock-down regulates the expression and alternative splicing of genes associated with Parkinson`s disease in U251 cells

Abstract

Eukaryotic Elongation Factor 1A1 (EEF1A1) is an RNA-binding protein that is associated with PARK2 activity in cells, predicting a possible important role in Parkinson`s disease (PD). However, it is not clear whether EEF1A1 will play a role in PD through transcriptional or post-transcriptional regulation. In this study, the GSE68719 data set was downloaded from the GEO database, and the RNA-seq data of BA9 brain tissue autopsy were obtained from 29 PD patients and 44 neurologically normal control subjects. The analysis found that EEF1A1 was significantly over-expressed in PD brain tissue. Then, to inhibit EEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells, and the RNA-seq high-throughput sequencing was used to determine the Differentially Expressed Genes (DEGs) and differentially alternative splicing events (ASEs) resulting from the EEF1A1 knockdown. Further, GO and KEGG enrichment analysis revealed that EEF1A1 knockdown significantly up-regulated the expression of genes CXCL10, NGF, PTX3, IL6, ST6GALNAC3, NUPR1, TNFRSF21, CXCL2, and up-regulated alternative splicing of genes ACOT7, DDX10, SHMT2, MYEF2, NDUFAF5. These genes were enriched to pathways related to PD pathogenesis, such as apoptosis, inflammatory response, and mitochondrial dysfunction, suggesting that EEF1A1 may be involved in the development of PD by regulating differential expression and alternative splicing of genes. This study preliminarily investigated the potential role and mechanism of EEF1A1 in the pathogenesis of PD, providing a theoretical basis for subsequent research.