Dataset Information

Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939.

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?, NF?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?B2 mRNAs, IL-6, VEGFA, and NOS2 proteins and NF?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.

SUBMITTER: McDonald MK

PROVIDER: S-EPMC4976376 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939.

McDonald Marguerite K MK Ramanathan Sujay S Touati Andrew A Zhou Yiqian Y Thanawala Rushi U RU Alexander Guillermo M GM Sacan Ahmet A Ajit Seena K SK

Scientific reports 20160808

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, TNFα, NFκB2, 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 vi ...[more]

PMID: 27498764

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Dataset Information

Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939.

Publications

Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939.

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