PRMT1影响胃癌PI3K-AKT通路基因表达的转录组分析

Transcriptome analysis of the effect of PRMT1 on PI3K-AKT pathway gene expression in gastric cancer

目的探讨胃癌中蛋白质精氨酸甲基转移酶1(PRMT1)对PI3K-AKT通路的基因表达的影响情况。方法转录组测序筛选2例胃癌及对应2例癌旁组织之间的差异表达基因,京都基因与基因组百科全书(KEGG)富集分析影响胃癌相关通路中的关键基因并利用免疫组化进行验证。结果高通量测序获得758个长度>200 bp的差异表达基因。KEGG富集分析表明25条显著富集代谢通路,其中PI3K-AKT代谢通路显著异常活化,共有15个基因显著上调;利用cBioportal数据库相关性分析,显示PRMT1与PI3K-AKT信号通路上的关键基因(PPP2R3A、THBS4)表达呈现负相关关系;免疫组化结果进一步表明低表达PRMT1的胃癌组织高表达p-AKT(473Ser),并且PRMT1与p-AKT(473Ser)呈现负相关关系,说明PRMT1与PI3K-AKT信号活性负相关。结论 PRMT1可能通过PPP2R3A、THBS4影响胃癌中PI3K-AKT信号通路的活性,为寻求胃癌诊断标志物及治疗靶点提供了线索。

Objective To investigate the effect of protein arginine methyltransferase(PRMT1)on gene expression of PI3 K-AKT pathway in gastric cancer.Methods The differentially expressed genes between 2 cases of gastric cancer and 2 cases of adjacent tissues were screened by transcriptome sequencing.The key genes affecting the pathway of gastric cancer were enriched and analyzed by kyoto gene encyclopedia of genome(KEGG)and verified by immunohistochemistry.Results 758 differentially expressed genes with length greater than 200 bp were obtained by high throughput sequencing.KEGG enrichment analysis revealed 25 significant enrichment metabolic pathways,of which PI3 K-AKT metabolic pathway was significantly abnormally activated containing 15 genes significantly up-regulated.cBioportal database correlation analysis showed that PRMT1 was negatively correlated with the expression of key genes(PPP2 R3 A,THBS4)in PI3 K-AKT signaling pathway.Immunohistochemical results further showed that there was a high expression of p-AKT(473 Ser)in gastric cancer tissues with low PRMT1 expression,moreover,there was a negative correlation between PRMT1 and p-AKT(473 Ser),indicating that PRMT1 was negatively correlated with PI3 K-AKT signal activity.Conclusion PRMT1 may affect the activity of PI3 K-AKT signaling pathway in gastric cancer through PPP2 R3 A and THBS4,which may provide clues for finding diagnostic markers and therapeutic targets of gastric cancer.