{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:13:41Z","timestamp":1791278021810,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2010,1,18]],"date-time":"2010-01-18T00:00:00Z","timestamp":1263772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cystic fibrosis (CF) is one of the most common lethal genetic diseases in which the role of microRNAs has yet to be explored. Predicted to be regulated by miR-126, TOM1 (target of Myb1) has been shown to interact with Toll-interacting protein, forming a complex to regulate endosomal trafficking of ubiquitinated proteins. TOM1 has also been proposed as a negative regulator of IL-1\u03b2 and TNF-\u03b1\u2013induced signaling pathways. MiR-126 is highly expressed in the lung, and we now show for the first time differential expression of miR-126 in CF versus non-CF airway epithelial cells both in vitro and in vivo. MiR-126 downregulation in CF bronchial epithelial cells correlated with a significant upregulation of TOM1 mRNA, both in vitro and in vivo when compared with their non-CF counterparts. Introduction of synthetic pre\u2013miR-126 inhibited luciferase activity in a reporter system containing the full length 3\u2032-untranslated region of TOM1 and resulted in decreased TOM1 protein production in CF bronchial epithelial cells. Following stimulation with LPS or IL-1\u03b2, overexpression of TOM1 was found to downregulate NF-\u03baB luciferase activity. Conversely, TOM1 knockdown resulted in a significant increase in NF-\u03baB regulated IL-8 secretion. These data show that miR-126 is differentially regulated in CF versus non-CF airway epithelial cells and that TOM1 is a miR-126 target that may have an important role in regulating innate immune responses in the CF lung. To our knowledge, this study is the first to report of a role for TOM1 in the TLR2\/4 signaling pathways and the first to describe microRNA involvement in CF.<\/jats:p>","DOI":"10.4049\/jimmunol.0902669","type":"journal-article","created":{"date-parts":[[2010,1,18]],"date-time":"2010-01-18T21:40:27Z","timestamp":1263850827000},"page":"1702-1709","source":"Crossref","is-referenced-by-count":172,"title":["miR-126 Is Downregulated in Cystic Fibrosis Airway Epithelial Cells and Regulates TOM1 Expression"],"prefix":"10.1093","volume":"184","author":[{"given":"Irene K","family":"Oglesby","sequence":"first","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella M","family":"Bray","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, Royal College of Surgeons in Ireland , Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay H","family":"Chotirmall","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond L","family":"Stallings","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, Royal College of Surgeons in Ireland , Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane J","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel G","family":"McElvaney","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M","family":"Greene","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,1,18]]},"reference":[{"key":"2026012806291799800_r1","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.4049\/jimmunol.174.3.1638","article-title":"TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells.","volume":"174","author":"Greene","year":"2005","journal-title":"J. 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