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Journal article
Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939
Scientific reports, v 6(1), pp 30976-30976
08 Aug 2016
PMID: 27498764
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Circulating microRNAs are beneficial biomarkers because of their stability and dysregulation in diseases. Here we sought to determine the role of miR-939, a miRNA downregulated in patients with complex regional pain syndrome (CRPS). Hsa-miR-939 is predicted to target several proinflammatory genes, including IL-6, VEGFA, TNF alpha, NF kappa B2, and nitric oxide synthase 2 (NOS2A). Binding of miR-939 to the 3' untranslated region of these genes was confirmed by reporter assay. Overexpression of miR-939 in vitro resulted in reduction of IL-6, NOS2A and NF kappa B2 mRNAs, IL-6, VEGFA, and NOS2 proteins and NF kappa B activation. We observed a significant decrease in the NOS substrate l-arginine in plasma from CRPS patients, suggesting reduced miR-939 levels may contribute to an increase in endogenous NOS2A levels and NO, and thereby to pain and inflammation. Pathway analysis showed that miR-939 represents a critical regulatory node in a network of inflammatory mediators. Collectively, our data suggest that miR-939 may regulate multiple proinflammatory genes and that downregulation of miR-939 in CRPS patients may increase expression of these genes, resulting in amplification of the inflammatory pain signal transduction cascade. Circulating miRNAs may function as crucial signaling nodes, and small changes in miRNA levels may influence target gene expression and thus disease.
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Details
- Title
- Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939
- Creators
- Marguerite K. McDonald - Drexel UniversitySujay Ramanathan - Drexel UniversityAndrew Touati - Drexel UniversityYiqian Zhou - Drexel UniversityRushi U. Thanawala - Drexel UniversityGuillermo M. Alexander - Drexel UniversityAhmet Sacan - Drexel UniversitySeena K. Ajit - Drexel University
- Publication Details
- Scientific reports, v 6(1), pp 30976-30976
- Publisher
- Springer Nature
- Number of pages
- 11
- Grant note
- NINDS 1R21NS082991-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Rita Allen Foundation R21NS082991 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems; [Retired Faculty]
- Web of Science ID
- WOS:000381457900001
- Scopus ID
- 2-s2.0-84981210537
- Other Identifier
- 991019168348704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology