类风湿性关节炎患者外周血单个核细胞MALAT1表达降低、 hsa-miR155-3p表达增加并参与Notch信号通路调节

Decreased long-chain non-coding RNA MALAT1 expression and increased hsa-miR155-3p expression involved in Notch signaling pathway regulation in rheumatoid arthritis patients

目的观察类风湿性关节炎(RA)患者长链非编码RNA(lncRNA)转移相关肺腺癌转录本1(MALAT1)、hsa-miR155-3p表达及其与Notch信号通路关系,探讨RA可能发病机制。方法采取RA患者(RA组)、健康对照者(NC组)外周血,采用高通量基因测序筛选差异表达的lncRNA和mRNA。利用反转录PCR检测筛选的lncRNA MALAT1和hsa-miR155-3p及Notch信号通路受体配体表达。结果通过lncRNA测序分析发现,共有9158条差异表达的lncRNA。基因本体(GO)功能分类注释得出差异表达的mRNA参与免疫炎症反应、细胞转录调节等。通过通路(pathway)分析显示差异表达的mRNA与免疫炎症、应激、Notch通路等功能基因变化有关。经顺式(Cis)和反式(Trans)预测,Jagged1/2、Delta1/2、Notch1/2可能与RA发生密切相关。与NC组相比,RA组MALAT1降低,hsa-miR155-3p明显升高;Notch通路配体Delta1、Delta2、Jagged1、Jagged2及受体Notch1、Notch2表达升高。相关性分析显示,hsa-miR155-3p与MALAT1呈负相关,hsa-miR155-3p与Notch通路Delta1、Jagged1呈正相关,MALAT1与Jagged2呈负相关。结论RA患者lncRNA MALAT1降低、hsa-miR155-3p增加,共同调节Notch信号通路变化。

Objective To observe the expression of long-chain non-coding RNA(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)and hsa-miR155-3p in patients with rheumatoid arthritis(RA)and their relationship with Notch signaling pathway,and to explore the possible pathogenesis of RA.Methods Peripheral blood of RA patients(RA group)and healthy controls(NC group)were used to screen differentially expressed lncRNA and mRNA by high-throughput gene sequencing.Reverse-transcription PCR was used to detect the expression of lncRNA MALAT1,hsa-miR155-3p and Notch signaling pathway receptor ligands.Results The lncRNA sequencing analysis showed a total of 9158 differentially expressed lncRNAs.Gene ontology(GO)functional classification annotations revealed that the differentially expressed mRNA was mainly involved in immune inflammatory response,cellular transcriptional regulation and so on.Pathway analysis proved that differentially expressed mRNA was significantly related to the genes involved in rheumatoid arthritis,cellular senescence,and Notch signaling pathways.According to cis and trans prediction,Jagged1-2,Delta1-2 and Notch1-2 might be closely related to RA.MALAT1 in the RA group was lower than that in the NC group,and hsa-miR155-3p expression was significantly higher than that in the NC group.The expression of Notch pathway ligands Delta1,Delta2 Jagged1,Jagged2 and the receptors Notch1 and Notch2 in the RA group increased.Correlation analysis showed that hsa-miR155-3p was inversely proportional to MALAT1,hsa-miR155-3p was directly proportional to Notch pathway Delta1,Jagged1,and MALAT1 was inversely proportional to Jagged2.Conclusion In patients with rheumatoid arthritis,lncRNA MALAT1 is reduced and hsa-mir155-3p is raised,which jointly regulate the change of Notch signaling pathway.