title: MicroRNA-203 accelerates apoptosis in LPS-stimulated alveolar epithelial cells by targeting PIK3CA.
abstract: The pathogenesis of endotoxin-induced acute lung injury (ALI) remains obscure and has not been well elucidated hitherto. Recently, microRNAs have distinct expression profiles in innate immunity, inflammation, and infection. However, the functions of microRNAs in ALI remain unknown. In this study, the functions of microRNAs in the development of ALI were investigated to identify potential drug targets. MicroRNA-203 (miR-203) expression in the lung tissues of lipopolysaccharide (LPS)-challenged mice was found to be significantly upregulated and peaked 5d post-LPS injection. MiR-203 overexpression in A549 cells significantly promoted cell apoptosis by inducing S-phase cell-cycle arrest. MiR-203 overexpression also inhibited the protein expression of phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA), a direct target of miR-203 identified by bioinformatics, thereby suppressing the PI3K/Akt pathway. Moreover, repressed miR-203 effectively attenuated LPS-induced interstitial pneumonia. Therefore, regulating or inhibiting miR-203 may be of therapeutic potential in pneumonia and ALI.
authors.affiliation: Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Xian-Fu
authors.initials: XF
authors.lastname: Ke
authors.affiliation: Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.affiliation: Zhejiang Medical College, Hangzhou 310053, China.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Wu
authors.affiliation: Zhejiang Academy of Medical Sciences, Hangzhou 310013, China. Electronic address: yuchenhuan2002@163.com.
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D058534:Class I Phosphatidylinositol 3-Kinases; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D008070:Lipopolysaccharides; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C575934:MIRN203 microRNA, mouse; C546639:Pik3ca protein, mouse
keywords: Apoptosis; Lipopolysaccharide; PIK3CA; microRNA-203