title: MicroRNA-449a levels increase by several orders of magnitude during mucociliary differentiation of airway epithelia.
abstract: MicroRNAs of the miR-34/449 family mediate cell cycle arrest and tumor suppression.  Here we show that the expression of microRNA miR-449a, unlike its paralogue miR-34a, is highly tissue specific and largely restricted to pulmonary and testicular tissue. MiR-449a levels in the murine lung are particularly high shortly before and after birth, coinciding with terminal differentiation of lung epithelia. Strikingly, miR-449a is upregulated by more than 1000-fold when epithelial cells from human airways are lifted from a liquid environment to air, allowing them to undergo mucociliary differentiation. The induction of miR-449a occurs in parallel to its host gene CDC20B and the transcription factor FoxJ1. Exposure to tobacco smoke induces a moderate further increase in the levels of miR-449a, and also miR-34a, in differentiated airway epithelia. We propose that miR-449a can serve as an exquisitely sensitive and specific biomarker for the differentiation of bronchial epithelia. Moreover, miR-449a may actively promote mucociliary differentiation through its ability to block cell cycle progression, and it may conribute to a first line of defence against genotoxic stress by its proapoptotic functions.
authors.affiliation: Department of Molecular Oncology, Göttingen Center of Molecular Biosciences, University of Göttingen, Germany.
authors.forename: Muriel
authors.initials: M
authors.lastname: Lizé
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.forename: Alexander
authors.initials: A
authors.lastname: Klimke
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.forename: Matthias
authors.initials: M
authors.lastname: Dobbelstein
mesh_terms: D000818:Animals; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D012907:Smoking
chemical_list: D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; C538721:Mirn449 microRNA, mouse