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The most common mutation F508del inhibits folding and processing of CFTR protein. FDA-approved correctors rescue the biosynthetic processing of F508del-CFTR protein, while potentiators improve the rescued CFTR channel function. Transforming growth factor (TGF-&amp;#x3B2;1), overexpressed in many CF patients, blocks corrector\/potentiator rescue by inhibiting CFTR mRNA in vitro. Increased TGF-&amp;#x3B2;1 signaling and acquired CFTR dysfunction are present in other lung diseases. To study the mechanism of TGF-&amp;#x3B2;1 repression of CFTR, we used molecular, biochemical, and functional approaches in primary human bronchial epithelial cells from over 50 donors. TGF-&amp;#x3B2;1 destabilized CFTR mRNA in cells from lungs with chronic disease, including CF, and impaired F508del-CFTR rescue by new-generation correctors. TGF-&amp;#x3B2;1 increased the active pool of selected micro(mi)RNAs validated as CFTR inhibitors, recruiting them to the RNA-induced silencing complex (RISC). Expression of F508del-CFTR globally modulated TGF-&amp;#x3B2;1-induced changes in the miRNA landscape, creating a permissive environment required for degradation of F508del-CFTR mRNA. In conclusion, TGF-&amp;#x3B2;1 may impede the full benefit of corrector\/potentiator therapy in CF patients. Studying miRNA recruitment to RISC under disease-specific conditions may help to better characterize the miRNAs utilized by TGF-&amp;#x3B2;1 to destabilize CFTR mRNA.<\/jats:p>","DOI":"10.3390\/ijms20194933","type":"journal-article","created":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T03:34:01Z","timestamp":1570419241000},"page":"4933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Transforming Growth Factor-\u03b21 Selectively Recruits microRNAs to the RNA-Induced Silencing Complex and Degrades CFTR mRNA under Permissive Conditions in Human Bronchial Epithelial Cells"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-0915","authenticated-orcid":false,"given":"Nilay","family":"Mitash","sequence":"first","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangping","family":"Mu","sequence":"additional","affiliation":[{"name":"Center for Research Computing, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua E.","family":"Donovan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Myerburg","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarangarajan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Pathology, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-2569","authenticated-orcid":false,"given":"Catherine M.","family":"Greene","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Swiatecka-Urban","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1146\/annurev.physiol.68.072304.112754","article-title":"Regulation of normal and cystic fibrosis airway surface liquid volume by phasic shear stress","volume":"68","author":"Tarran","year":"2006","journal-title":"Annu. 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