%0 Journal Article %A Oglesby, Irene K. %A Agrawal, Raman %A Mall, Marcus A. %A McElvaney, Noel G. %A Greene, Catherine M. %D 2019 %T miRNA-221 is elevated in cystic fibrosis airway epithelial cells and regulates expression of ATF6. %U https://repository.rcsi.com/articles/journal_contribution/miRNA-221_is_elevated_in_cystic_fibrosis_airway_epithelial_cells_and_regulates_expression_of_ATF6_/10784903 %2 https://repository.rcsi.com/ndownloader/files/19297994 %K ATF6 %K Cystic fibrosis %K miRNA-221 %K Medicine %X
Using in silico analysis, miRNAs predicted to target the 3′untranslated region (3′UTR) of the human ATF6 mRNA were identified.
Three 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.
These 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.
%I Royal College of Surgeons in Ireland