@article {Magnaye2003862, author = {Kevin M. Magnaye and Katherine A. Naughton and Janel Huffman and D. Kyle Hogarth and Edward T. Naureckas and Steven R. White and Carole Ober}, title = {A-to-I editing of miR-200b-3p in airway cells is associated with moderate-to-severe asthma}, elocation-id = {2003862}, year = {2021}, doi = {10.1183/13993003.03862-2020}, publisher = {European Respiratory Society}, abstract = {Background Asthma is a chronic lung disease characterised by persistent airway inflammation. Altered microRNA-mediated gene silencing in bronchial epithelial cells has been reported in asthma, yet ADAR-mediated microRNA editing in asthma remains unexplored.Methods We first identified A-to-I edited sites in microRNAs in bronchial epithelial cells from 142 adult asthma cases and controls. A-to-I edited sites were tested for associations with asthma severity and clinical measures of asthma. Paired RNA-seq data was used to perform pathway enrichments and test for associations with bioinformatically predicted target genes of the unedited and edited microRNAs.Results Of 19 A-to-I edited sites detected in these microRNAs, one site at position 5 of miR-200b-3p was edited less frequently in cases compared to controls (p=0.013), and especially compared to cases with moderate (p=0.029) and severe (p=3.9{\texttimes}10-4), but not mild (p=0.38), asthma. Bioinformatic prediction revealed 232 target genes of the edited miR-200b-3p, which were enriched for both IL-4 and interferon gamma signalling pathways and included the SOCS1 (suppressor of cytokine signalling 1) gene. SOCS1 was more highly expressed in moderate (p=0.017) and severe (p=5.4{\texttimes}10-3) asthma cases compared to controls. Moreover, both miR-200b-3p editing and SOCS1 were associated with BAL eosinophil levels.Conclusion Reduced A-to-I editing of the 5th position of miR-200b-3p in lower airway cells from moderate-to-severe asthmatics may lead to overexpression of SOCS1 and impaired cytokine signalling. We proposed ADAR-mediated editing as an epigenetic mechanism contributing to features of moderate-to-severe asthma in adulthood.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Funke-Chambour reports grants from roche, grants and personal fees from Boehringer Ingelheim, outside the submitted work;. Dr. Funke-Chambour reports grants from roche, grants and personal fees from Boehringer Ingelheim, outside the submitted work;.Conflict of interest: Dr. Magnaye reports In addition, Dr. Magnaye has a patent {\textquotedblleft}ADAR-Mediated MiRNA Editing in Asthma{\textquotedblright} (63011935) pending.Conflict of interest: Dr. Naughton has nothing to disclose.Conflict of interest: Dr. Huffman has nothing to disclose.Conflict of interest: Dr. Hogarth reports personal fees from Olympus/Spiration, personal fees from PulmonX, during the conduct of the study; personal fees and other from Auris, personal fees from Ambu, personal fees, non-financial support and other from Body Vision, personal fees and other from Eolo, other from Eon, other from Gravitas, personal fees and other from Noah Medical, personal fees and other from LX-Medical, other from Med-Opsys, other from Monogram Orthopedics, personal fees and other from Preora, other from VIDA, other from Viomics, grants and personal fees from Boston Scientific, personal fees from Johnson and Johnson, personal fees from oncocyte, personal fees from veracyte, personal fees and other from Broncus, grants and personal fees from Gala, personal fees from Heritage Biologics, personal fees from IDbyDNA, personal fees from Level-Ex, personal fees from Medtronic, personal fees from Neurotronic, personal fees from olympus, personal fees from PulmonX, personal fees from Astra-Zeneca, personal fees from Biodesix, personal fees from Genetech, personal fees from Grifols, personal fees from Takeda, personal fees from CSL, personal fees from InhibRX, personal fees and other from Prothea-X, outside the submitted work.Conflict of interest: Dr. Naureckas has nothing to disclose.Conflict of interest: Dr. White reports In addition, Dr. White has a patent {\textquotedblleft}ADAR-Mediated MiRNA Editing in Asthma{\textquotedblright} (63011935) pending.Conflict of interest: Dr. Ober reports In addition, Dr. Ober has a patent {\textquotedblleft}ADAR-Mediated MiRNA Editing in Asthma{\textquotedblright} (63011935) pending.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/early/2021/01/08/13993003.03862-2020}, eprint = {https://erj.ersjournals.com/content/early/2021/01/08/13993003.03862-2020.full.pdf}, journal = {European Respiratory Journal} }