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

Chao Fang  ¹ , Weihong Lu  ¹ , Chengyan Li  ¹ , Xi Peng  ¹ , Yang Wang  ² , Xiulan Huang  ¹ , Zhihong Yao  ¹ , Nali Cai  ¹ , Yuge Huang  ¹ , Xingliang Zhang  ¹ , Jianxin Tan  ¹

Affiliations

• ¹ Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
• ² Department of Biomedical Research, National Jewish Health, Denver, Colorado, 80206, United States of America.

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 β-catenin. Luciferase assays and western blot analysis confirmed β-catenin as a direct target of miR-3162-3p as the 3′-untranslated region of β-catenin mRNA possesses a specific miR-3162-3p pairing site. The correlation between the expression levels of miR-3162-3p and β-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 β-catenin mRNA and protein expression levels. MiR-3162-3p antagomir treatment antagonizes the endogenous miR-3162-3p and effectively rescues the attenuation of endogenous β-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 β-catenin and clarify their mechanistic role in asthma etiopathogenesis.