NovelmiRNA-25 inhibits AMPD2 in peripheral blood mononuclear cells of patients with systemic lupus erythematosus and represents a promising novel biomarker

Systemic 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 metabo...

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Published in:	Journal of translational medicine 2018-12, Vol.16 (1), p.370-370, Article 370
Main Authors:	Guo, Gangqiang, Wang, Huijing, Shi, Xinyu, Ye, Lele, Wu, Kai, Lin, Kangmin, Ye, Sisi, Li, Baoqing, Zhang, Huidi, Lin, Qiaoai, Ye, Shuang, Xue, Xiangyang, Chen, Chaosheng
Format:	Article
Language:	eng
Subjects:	Adenosine Adenosine deaminase Adenosine monophosphate AMP AMP Deaminase - blood AMPD2 Analysis Autoimmune diseases Base Sequence Bioindicators Bioinformatics Biological markers Biomarker Biomarkers Biomarkers - blood Blood Case-Control Studies Chronic conditions Diagnostic systems Gene expression Gene Ontology Gene Regulatory Networks HEK293 Cells Humans Leukocytes (mononuclear) Leukocytes, Mononuclear - metabolism Lupus Lupus Erythematosus, Systemic - blood Lupus Erythematosus, Systemic - genetics Lymphocytes Metabolism MicroRNA MicroRNAs MicroRNAs - metabolism miRNA Next-generation sequencing Pathogenesis Patients Peripheral blood mononuclear cells Predictive control Protein expression Proteins Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism RNA-sequencing SLE Systemic lupus erythematosus Therapeutic applications Transcription
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Summary:	Systemic 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. We 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. Multilayer 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
ISSN:	1479-5876 1479-5876