Type

Other / n/a

Authors

Catherine M Greene
Noel G McElvaney
Marcus A Mall
Raman Agrawal
Irene K Oglesby

Subjects

Microbiology

Topics
messenger rna mrna transcription factor medicine and health sciences atf6 epithelial cells mirna 221 lung disease cystic fibrosis

miRNA-221 is elevated in cystic fibrosis airway epithelial cells and regulates expression of ATF6. (2015)

Abstract Background MicroRNA (miRNA) and messenger RNA (mRNA) expression differs in cystic fibrosis (CF) versus non-CF bronchial epithelium. Here, the role of miRNA in basal regulation of the transcription factor ATF6 was investigated in bronchial epithelial cells in vitro and in vivo. MethodsUsing in silico analysis, miRNAs predicted to target the 3′untranslated region (3′UTR) of the human ATF6 mRNA were identified. ResultsThree of these miRNAs, miR-145, miR-221 and miR-494, were upregulated in F508del-CFTR homozygous CFBE41o- versus non-CF 16HBE14o- bronchial epithelial cells and also in F508del-CFTR homozygous or heterozygous CF (n = 8) versus non-CF (n = 9) bronchial brushings. ATF6 was experimentally validated as a molecular target of these miRNAs through the use of a luciferase reporter vector containing the full-length 3′UTR of ATF6. Expression of ATF6 was observed to be decreased in CF both in vivo and in vitro. miR-221 was also predicted to regulate murine ATF6, and its expression was significantly increased in native airway tissues of 6-week-old βENaC-overexpressing transgenic mice with CF-like lung disease versus wild-type littermates. ConclusionsThese results implicate miR-145, miR-221 and miR-494 in the regulation of ATF6 in CF bronchial epithelium, with miR-221 demonstrating structural and functional conservation between humans and mice. The altered miRNA expression evident in CF bronchial epithelial cells can affect expression of transcriptional regulators such as ATF6.
Collections Ireland -> Royal College of Surgeons in Ireland -> Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Medicine

Full list of authors on original publication

Catherine M Greene, Noel G McElvaney, Marcus A Mall, Raman Agrawal, Irene K Oglesby

Experts in our system

1
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
2
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
3
Marcus A Mall
Royal College of Surgeons in Ireland
Total Publications: 4