EPRS1通过影响趋化因子的表达与功能促进肝癌细胞的恶性表型

EPRS1 Promotes the Malignant Phenotype of Hepatocellular Carcinoma by Affecting the Expression and Function of Chemokines

目的:探讨谷氨酰脯氨酰t RNA合成酶在人肝细胞癌中促癌的潜在机制。方法:siRNA抑制Hep3B细胞中EPRS1的表达,RNA-seq检测其与对照组之间的差异基因,TCGA-LIHC数据集中验证,GO和GSEA分析差异基因参与的细胞生物学过程。结果:检测差异基因304个,其中上调基因98个(32.2%),下调基因206个(67.8%),GO分析提示下调基因主要的分子功能是影响CXCLR受体结合和趋化因子活化。GSEA分析提示随着EPRS1的降低细胞因子与其受体的相互作用相关通路受到影响。而在基因表达水平层面发现趋化因子家族中的5种基因表达水平下降,在TCGA-LIHC数据集中分析表明其中CXCL5和CCL20在肝癌样本中高表达(P<0.05),且与EPRS1表达水平呈正相关。结论:EPRS1通过提高多种趋化因子的表达并影响趋化因子与其受体结合过程发挥促癌作用。

Objective:Investigate the potential mechanism of glutamyl-prolyl-tRNA synthase in promoting human hepatocellular carcinoma.Methods:SiRNA inhibited the expression of EPRS1 in Hep3B cells,RNA-seq detected the differential genes between Hep3B cells and the control group.Validated in the TCGA-LIHC dataset.GO and GSEA enrichment analyzed the cellular biological processes involved in the differential genes.Results:There were 304 difference gene,which includes an increase of 98(32.2%)genes and a reduction of 206(67.8%)genes.GO analysis suggested that the main molecular function of the reduction of the gene was mainly to affect the combination of CXCLR receptor and chemokine activation.The GSEA analysis suggests that the reduce of the expression of EPRS1 affects the pathway of cytokine-cytokine receptor interaction.In gene expression,we found that the expression of CX3CL1/CXCL3/CXCL5/CXCL8/CCL20 was decreased.Analysis of their expression in TCGA-LIHC dataset suggested that CXCL5 and CCL20 were highly expressed in HCC samples(P<0.05),and were positively correlated with EPRS1 expression.Conclusions:EPRS1 promotes the progression of HCC by enhancing the expression and function of chemokines.