MiR-3162-3p Is a Novel MicroRNA That Exacerbates Asthma by Regulating ?-Catenin.

ABSTRACT: Asthma is a common chronic respiratory disease. In a previous study, we found several circulating microRNA signatures associated with childhood asthma and selected miR-3162-3p for subsequent studies. Since the target proteins and underlying molecular mechanisms of miR-3162-3p in asthma etiopathogenesis are not well characterized, we designed this study to clarify its role. We employed bioinformatics and quantitative PCR methods as a first step to determine the target of miR-3162-3p, and we elucidated ?-catenin. Luciferase assays and western blot analysis confirmed ?-catenin as a direct target of miR-3162-3p as the 3'-untranslated region of ?-catenin mRNA possesses a specific miR-3162-3p pairing site. The correlation between the expression levels of miR-3162-3p and ?-catenin is confirmed by quantitative PCR and western blot studies in A549, Beas-2B and H1299 cell lines and OVA-induced asthma mouse model. Of note, upregulation of the endogenous miR-3162-3p level is concomitant with the reduction of ?-catenin mRNA and protein expression levels. MiR-3162-3p antagomir treatment antagonizes the endogenous miR-3162-3p and effectively rescues the attenuation of endogenous ?-catenin in OVA-induced asthmatic mice, which alleviates airway hyperresponsiveness and ameliorates airway inflammation. Collectively, our findings suggest a novel relationship between miR-3162-3p and ?-catenin and clarify their mechanistic role in asthma etiopathogenesis.

SUBMITTER: Fang C 

PROVIDER: S-EPMC4784915 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature