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

• 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: English
• Subjects: Adenosine; Adenosine deaminase; AMP; AMP Deaminase - blood; AMPD2; Analysis; Autoimmune diseases; Base Sequence; Bioindicators; Bioinformatics; Biological markers; Biomarker; Biomarkers; Biomarkers - blood; Case-Control Studies; Chronic conditions; 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; Protein expression; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-sequencing; SLE; Systemic lupus erythematosus; Therapeutic applications; Transcription
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-018-1739-5

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