NovelmiRNA-25 inhibits AMPD2 in peripheral blood mononuclear cells of patients with systemic lupus erythematosus and represents a promising novel biomarker
NovelmiRNA-25 inhibits AMPD2 in peripheral blood mononuclear cells of patients with systemic lupus erythematosus and represents a promising novel biomarker
复制标题
DOI：
10.1186/s12967-018-1739-5
复制
发表时间：
2018-12-22
影响因子：
7.4
通讯作者：
Chen, Chaosheng
中科院分区：
文献类型：
--
作者：
Guo, Gangqiang;Wang, Huijing;Chen, Chaosheng
研究背景系统性红斑狼疮（SLE）是一种临床表现多样的多系统自身免疫性疾病。microRNAs（miRNAs）和免疫代谢被认为是SLE发病机制中的关键因素;然而，外周血单个核细胞（PBMC）中的miRNA与SLE代谢之间的关系仍不清楚。方法我们使用下一代测序检测来自3名合并的SLE患者和3名健康对照（HC）的PBMC miRNA和mRNA谱，预测失调mRNA中的miRNA靶，利用生物信息学分析预测差异表达基因的功能和相互作用，利用qRT-PCR验证候选miRNAs，并研究候选miRNAs的表达与SLE临床特征之间的关系。此外，我们使用双荧光素酶报告基因测定和western印迹验证了NovelmiRNA-25对腺苷酸脱氨酶2（AMPD 2）的直接和转录调节作用，并使用qRT-PCR和western印迹证实了PBMC中AMPD 2 mRNA和蛋白质的表达，结果microRNA和mRNA调控的多层整合分析显示，10个miRNAs下调，19个miRNAs上调。与HC相比，SLE患者PBMCs中的调节。通过对miRNAs和mRNAs之间调控网络的生物信息学分析，发现19个miRNAs与代谢过程相关。两种候选miRNAs NovelmiRNA-25和miR-1273 h-5 p在SLE患者PBMC中表达显著增加（P
BackgroundSystemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with various clinical manifestations. MicroRNAs (miRNAs) and immunometabolism are recognized as key elements in SLE pathogenesis; however, the relationship between miRNAs in peripheral blood mononuclear cells (PBMCs) and metabolism in SLE remains unclear.MethodsWe detected PBMC miRNA and mRNA profiles from 3 pooled SLE patients and 3 healthy controls (HCs) using next-generation sequencing, predicted miRNA targets in dysregulated mRNAs, predicted functions and interactions of differentially expressed genes using bioinformatics analysis, validated candidate miRNAs using qRT-PCR, and investigated the association between the expression of candidate miRNAs and SLE clinical characteristics. Moreover, we validated the direct and transcriptional regulatory effect of NovelmiRNA-25 on adenosine monophosphate deaminase 2 (AMPD2) using a dual-luciferase reporter assay and western blot and confirmed AMPD2 mRNA and protein expression in PBMCs using qRT-PCR and western blot, respectively.ResultsMultilayer integrative analysis of microRNA and mRNA regulation showed that 10 miRNAs were down-regulated and 19 miRNAs were up-regulated in SLE patient PBMCs compared with HCs. Bioinformatics analysis of regulatory networks between miRNAs and mRNAs showed that 19 miRNAs were related to metabolic processes. Two candidate miRNAs, NovelmiRNA-25 and miR-1273h-5p, which were significantly increased in the PBMCs of SLE patients (P