miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo.

Abstract

OBJECTIVE:

Nuclear factor kappa-B (NF-954;B)-induced inflammation leads to myocarditis and heart dysfunction. How microRNAs (miRNAs) contribute to this process is poorly defined. The aim of this study was to investigate whether miRNAs regulate NF-954;B-induced inflammation in experimental autoimmune myocarditis (EAM) in vivo.

METHODS AND RESULTS:

NF-954;B and its related proinflammatory genes, including interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), were activated in EAM. Profiling of NF-954;B-related miRNAs revealed that miR-590-3p was strikingly reduced in EAM. We found IL-6-induced proinflammatory signaling via miR-590-3p reduction, p50 induction, NF-954;B activation and IL-6/TNF-a expression. Moreover, a luciferase reporter assay demonstrated that miR-590-3p directly interacted with the 3' UTR (untranslated region) of the p50 subunit, and that miR-590-3p overexpression inhibited p50 expression. Finally, miR-590-3p transfection through adeno-associated virus significantly inhibited p50 expression, suppressed NF-954;B activity and blocked IL-6/TNF-a expression in vivo, reducing the lesion area and improving cardiac function in EAM.

CONCLUSION:

miR-590-3p is a novel NF-954;B-related miRNA that directly targets the p50 subunit. This may provide a novel strategy for the treatment of myocarditis.

• Authors: Sijia Zhao, Guang Yang, Pei-Ning Liu, Yang-Yang Deng, Zhao Zhao, Tao Sun, Xiao-Zhen Zhuo, Jun-Hui Liu, Yuling Tian, Juan Zhou, Zuyi Yuan, Yue Wu
• Journal: Cardiology (Cardiology) Vol. 132 Issue 3 Pg. 182-8 ( 2015) ISSN: 1421-9751 [Electronic] Switzerland
• PMID: 26278103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Interleukin-6
• MicroRNAs
• NF-kappa B p50 Subunit
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Interleukin-6 (genetics)
• Male
• MicroRNAs (genetics)
• Myocarditis (genetics)
• NF-kappa B p50 Subunit (genetics)
• Rats
• Tumor Necrosis Factor-alpha (genetics)