title: MiR-3162-3p Is a Novel MicroRNA That Exacerbates Asthma by Regulating β-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 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.
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, Colorado, 80206, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Nali
authors.initials: N
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Yuge
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Tan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001249:Asthma / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D001483:Base Sequence; D002460:Cell Line; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000494:pharmacology; D010047:Ovalbumin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C000609290:MIRN-3162 microRNA, human; C000609291:MIRN-3162 microRNA, mouse; D035683:MicroRNAs; D009841:Oligonucleotides; D012333:RNA, Messenger; D051176:beta Catenin; D010047:Ovalbumin