miR-330 regulates interleukin-13-induced MUC5AC secretion by targeting Munc18b in human bronchial epithelial cells.

Mucus hypersecretion by airway epithelium and plugging of the airways are primary reasons of mortality in asthma patients and major causes of asthma disease progression and exacerbation. MUC5AC protein is a major component of airway mucus. MicroRNAs (miRNAs), a class of small noncoding RNAs, have emerged as moderators of MUC5AC production and secretion and are implicated in the pathogenesis of asthma. Recently, miR-330 has been reported to be downregulated in the blood of asthmatic patients, acting as a biomarker for asthma. The role of miR-330 in asthma, however, is unclear. Here, we showed that interleukin (IL)-13 induced MUC5AC secretion and inhibited miR-330 expression in a concentration-dependent manner in human bronchial epithelial cells (HBE16). Upregulation of miR-330 in HBE16 cells inhibited IL-13-induced MUC5AC secretion while, conversely, depletion of endogenous miR-330 exacerbated MUC5AC secretion. Munc18b (Syntaxin-Binding Protein 2; STXBP2) is a limiting component of the exocytic machinery of airway epithelial cells. We identified and validated that Munc18b was a direct target of miR-330 and miR-330 regulated MUC5AC secretion in HBE16 cells by acting directly on the 3'UTR of Munc18b mRNA. Collectively, these data reveal that miR-330 inhibits IL-13-induced MUC5AC secretion in human bronchial epithelial cells by targeting Munc18b, encouraging us to further explore the potential of manipulating miR-330 in treatment of airway diseases with mucus hypersecretion.