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



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.



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.
Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.
Sijia
S
Zhao
Guang
G
Yang
Pei-Ning
PN
Liu
Yang-Yang
YY
Deng
Zhao
Z
Zhao
Tao
T
Sun
Xiao-Zhen
XZ
Zhuo
Jun-Hui
JH
Liu
Yuling
Y
Tian
Juan
J
Zhou
Zuyi
Z
Yuan
Yue
Y
Wu
D000818:Animals; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009205:Myocarditis / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015850:Interleukin-6; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; D014409:Tumor Necrosis Factor-alpha