title: Ectopic expressed miR-203 contributes to chronic obstructive pulmonary disease via targeting TAK1 and PIK3CA.
abstract: MiRNA is a group of powerful short non-coding RNAs that suppress the expression of protein coding genes by targeting to the 3'UTRs of mRNAs. Some researchers have detected the miRNAs expression profile in tissue and blood samples of chronic obstructive pulmonary disease (COPD) patients recently. Several disturbed miRNAs were found to be related to COPD; however, the mechanisms were still well understood. In this study, we first detected the expression of 11 candidate miRNAs in the lung samples of COPD patients, non-COPD smokers and non-smock controls. We found that the expression of miR-181a, miR-203, miR-338, miR-1 and miR-199a was altered compared with control. Subsequently, we detected these five miRNAs expression in the blood samples of the participants. A significant higher expression of miR-203 was found in the blood samples of smokers and COPD patients. Predicted by bioinformatics tools and confirmed by luciferase assay and western blot, we demonstrated that TAK1 and PIK3CA are two direct targets of miR-203. Furthermore, we detected a lower p-IκBα and p-p65 level in the bronchial/tracheal epithelial cells from COPD patients compared with the cells from healthy controls, when stimulated by LPS. The concentration of TNF-α and IL-6 in the medium from bronchial/tracheal epithelial cells from COPD patients is also lower. Meanwhile, the miR-203 level was down-regulated significantly in the control cells, but non-significant change in the cells from COPD patients. miR-203 represses NF-κB signaling via targeting TAK1 and PI3KCA and miR-203 overexpression may contribute to the COPD initiation.
authors.affiliation: Department of Respiratory Disease, Chinese PLA General Hospital Beijing 100853, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Respiratory Disease, General Hospital of Beijing PLA Military Region Beijing 100700, China.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Xin
authors.affiliation: Department of Respiratory and Critical Care Medicine, General Hospital of Shenyang PLA Military Region Shenyang, Liaoning 110016, China.
authors.forename: Ruonan
authors.initials: R
authors.lastname: Chai
authors.affiliation: Department of Respiratory and Critical Care Medicine, General Hospital of Shenyang PLA Military Region Shenyang, Liaoning 110016, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, General Hospital of Shenyang PLA Military Region Shenyang, Liaoning 110016, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001980:Bronchi / Q000201:enzymology*; D016022:Case-Control Studies; D058534:Class I Phosphatidylinositol 3-Kinases; D004847:Epithelial Cells / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019169:Jurkat Cells; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020413:3' Untranslated Regions; D058534:Class I Phosphatidylinositol 3-Kinases; D020672:I-kappa B Proteins; D015850:Interleukin-6; D020930:MAP Kinase Kinase Kinases; D035683:MicroRNAs; D000072000:NF-KappaB Inhibitor alpha; D019869:Phosphatidylinositol 3-Kinases; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C508600:IL6 protein, human; C546703:MIRN203 microRNA, human; C000606204:NFKBIA protein, human; C498143:RELA protein, human; C484760:PIK3CA protein, human
keywords: MicroRNA; NF-κB; chronic obstructive pulmonary disease