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In this study we wanted to identify<jats:italic>trans<\/jats:italic>-regulatory elements responsible for<jats:italic>CFTR<\/jats:italic>differential expression in fetal and adult lung, and to determine the importance of inhibitory motifs in the<jats:italic>CFTR<\/jats:italic>-3\u2032UTR with the aim of developing new tools for the correction of disease-causing mutations within<jats:italic>CFTR<\/jats:italic>.<\/jats:p><jats:p>We show that lung development-specific transcription factors (FOXA, C\/EBP) and microRNAs (miR-101, miR-145, miR-384) regulate the switch from strong fetal to very low<jats:italic>CFTR<\/jats:italic>expression after birth. By using miRNome profiling and gene reporter assays, we found that miR-101 and miR-145 are specifically upregulated in adult lung and that miR-101 directly acts on its cognate site in the<jats:italic>CFTR<\/jats:italic>-3\u2032UTR in combination with an overlapping AU-rich element. We then designed miRNA-binding blocker oligonucleotides (MBBOs) to prevent binding of several miRNAs to the<jats:italic>CFTR<\/jats:italic>-3\u2032UTR and tested them in primary human nasal epithelial cells from healthy individuals and CF patients carrying the p.Phe508del<jats:italic>CFTR<\/jats:italic>mutation. These MBBOs rescued CFTR channel activity by increasing CFTR mRNA and protein levels.<\/jats:p><jats:p>Our data offer new understanding of the control of the<jats:italic>CFTR<\/jats:italic>gene regulation and new putative correctors for cystic fibrosis.<\/jats:p>","DOI":"10.1183\/09031936.00113214","type":"journal-article","created":{"date-parts":[[2014,9,4]],"date-time":"2014-09-04T13:33:01Z","timestamp":1409837581000},"page":"116-128","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":82,"title":["Transcription factors and miRNAs that regulate fetal to adult<i>CFTR<\/i>expression change are new targets for cystic fibrosis"],"prefix":"10.1183","volume":"45","author":[{"given":"Victoria","family":"Viart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bergougnoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Bonini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Varilh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Chiron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Tabary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Molinari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Claustres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Taulan-Cadars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2014,9,3]]},"reference":[{"key":"2024102023014511000_45.1.116.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.8.080706.092323"},{"key":"2024102023014511000_45.1.116.2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200800212"},{"key":"2024102023014511000_45.1.116.3","doi-asserted-by":"crossref","first-page":"762","DOI":"10.18632\/aging.100085","article-title":"Coupling transcriptional and post-transcriptional miRNA regulation in the control of cell fate","volume":"1","author":"Shalgi","year":"2009","journal-title":"Aging (Albany NY)"},{"key":"2024102023014511000_45.1.116.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2843"},{"key":"2024102023014511000_45.1.116.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010854"},{"key":"2024102023014511000_45.1.116.6","doi-asserted-by":"crossref","first-page":"24471","DOI":"10.1016\/S0021-9258(18)54252-6","article-title":"Characterization of the promoter region of the cystic fibrosis transmembrane conductance regulator gene","volume":"266","author":"Chou","year":"1991","journal-title":"J Biol Chem"},{"key":"2024102023014511000_45.1.116.7","doi-asserted-by":"crossref","first-page":"9140","DOI":"10.1016\/S0021-9258(18)31562-X","article-title":"The cystic fibrosis gene has a \u201chousekeeping\u201d-type promoter and is expressed at low levels in cells of epithelial origin","volume":"266","author":"Yoshimura","year":"1991","journal-title":"J Biol Chem"},{"key":"2024102023014511000_45.1.116.8","doi-asserted-by":"crossref","first-page":"15912","DOI":"10.1016\/S0021-9258(18)82339-0","article-title":"Characterization of the cystic fibrosis transmembrane conductance regulator promoter region. 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