miroRNA-31 affects the expression of asthma-related cytokines via regulation of CD44

作者:Li, Ling; Hui, Yu; Xing, Chaofeng; Guo, Yun; Wang, Qian; Shu, Jin; Qian, Jun*; Zhou, Guoping*
来源:International Journal of Clinical and Experimental Medicine, 2016, 9(11): 21506-21513.

摘要

MiroRNAs (miRNAs) play a crucial role in inflammatory development and the progression of asthma. In this study, we aimed to identify miRNAs that regulate gene expression of CD44, an asthma-related inflammatory factor, by targeting CD44 promoter elements and to analyse the role of miRNAs in asthma. Bioinformatic analysis was performed to predict miRNAs that potentially regulate gene expression of CD44 by binding to the CD44 promoter. The expression of these miRNAs was detected in epithelial cells and plasma in both asthma patients and healthy controls. We then transfected the relevant miRNA mimic/inhibitor into human bronchial epithelial cells; measured the expression of CD44 using real-time quantitative polymerase chain reaction (qPCR), immunoblotting (Western blot) and cellular immunofluorescence; and detected asthma-related cytokine (IL-6, IL-8 and ICAM) expression levels by ELISA. We first identified that miR-31 expression was enhanced in the epithelial cells and plasma of asthma patients. In vitro, our data indicated that overexpression of miR-31 induced the expression level of CD44 and enhanced asthma-related cytokines in BEAS-2B cells, while knockdown of endogenous miR-31 decreased CD44 and asthma-related cytokine levels. Further studies demonstrated that miR-31 regulated the progression of asthma by directly binding the promoter region of the CD44 gene and that re-suppression and restoration of CD44 expression reversed the effects of miR-31 on expression of asthma-related cytokines. Taken together, our findings indicate that miR-31 may play a valuable role in the asthma-related inflammatory response and may be a promising interventional therapeutic target for asthma.