Regulation of microRNA-155 in Endothelial Inflammation by Targeting Nuclear Factor (NF)-κB P65

• Published in: Journal of cellular biochemistry 2014-11, Vol.115 (11), p.1928-1936
• Main Authors: Wu, Xiao-Yuan, Fan, Wen-Dong, Fang, Rong, Wu, Gui-Fu
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Cytokines - metabolism; ENDOTHELIAL INFLAMMATION; HEK293 Cells; Human Umbilical Vein Endothelial Cells; Humans; Inflammation - genetics; Inflammation - metabolism; microRNA 155; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Biological; NFкB P65; TNFα; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.24864

ABSTRACT Increasing evidences have illuminated the fundamental role of inflammation in mediating all stages of atherosclerosis. miR‐155, a typical multi‐functional miRNA, has recently emerged as a novel component of inflammatory signal transduction in the pathogenesis of atherosclerosis. However, little is known about whether endothelial highly expressed miR‐155 can regulate endothelial inflammation‐related transcription factors and the predicted role of miR‐155 as a negative feedback regulator in endothelial inflammation involved in atherosclerosis. Bioinformatics analysis showed that RELA (nuclear factor‐κB p65) is a potential target gene of miR‐155 and this was confirmed by a luciferase reporter assay. Our results show that microRNA‐155 mediate endothelial inflammation and decrease NFкB p65 and adhesion molecule expression in TNFα‐stimulated endothelial cells. Transfection with miR‐155 significantly inhibited TNFα‐induced monocyte adhesion to endothelium. Inhibition of miR‐155 enhanced p65 level and endothelial inflammatory response which was counteracted through the depletion of P65 by Si‐P65. On the other hand, knockdown of eNOS, another target of miR‐155, while transfecting with miR‐155 inhibitor resulted in more significant inflammatory response. miR‐155 is highly expressed in TNFα treated HUVECs, deprived of endogenous p65 could reverse TNFα‐induced upregulation of miR‐155. Thus, TNFα induced miR‐155 may serve as a negative feedback regulator in endothelial inflammation involved in atherosclerosis by targeting nuclear transcription factor P65. These results provide a rationale for intervention of intracellular microRNA as possible anti‐atherosclerotic targets. J. Cell. Biochem. 115: 1928–1936, 2014. © 2014 Wiley Periodicals, Inc.