title: Identification of miRNAs Potentially Involved in Bronchiolitis Obliterans Syndrome: A Computational Study.
abstract: The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs-miR-34a and miR-21 -was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline.
authors: Control and Computer Engineer Department, Politecnico di Torino, Torino, Italy.
authors: Stefano
authors: http://orcid.org/0000-0002-7512-5356
authors: S
authors: Di Carlo
authors: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors: Elena
authors: E
authors: Rossi
authors: Control and Computer Engineer Department, Politecnico di Torino, Torino, Italy.
authors: Gianfranco
authors: G
authors: Politano
authors: Department of Respiratory Diseases IRCCS Policlinico S. Matteo, Pavia, Italy.
authors: Simona
authors: S
authors: Inghilleri
authors: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors: Patrizia
authors: P
authors: Morbini
authors: Department of Cardiovascular and Thoracic Sciences, University of Padova, Padova, Italy.
authors: Fiorella
authors: F
authors: Calabrese
authors: Control and Computer Engineer Department, Politecnico di Torino, Torino, Italy.
authors: Alfredo
authors: A
authors: Benso
authors: Control and Computer Engineer Department, Politecnico di Torino, Torino, Italy.
authors: Alessandro
authors: A
authors: Savino
authors: Department of Respiratory Diseases IRCCS Policlinico S. Matteo, Pavia, Italy.
authors: Emanuela
authors: E
authors: Cova
authors: Thoracic Surgery Unit, Department Cardiothoracic and Vascular Sciences, University of Padova, Medical School, Padova, Italy.
authors: Davide
authors: D
authors: Zampieri
authors: Department of Internal Medicine, University of Pavia, Pavia, Italy.|Department of Respiratory Diseases IRCCS Policlinico S. Matteo, Pavia, Italy.
authors: Federica
authors: F
authors: Meloni
mesh_terms: D000072283:A549 Cells; D000208:Acute Disease; D000465:Algorithms; D000818:Animals; D001989:Bronchiolitis Obliterans / Q000235:genetics*; D002908:Chronic Disease; D003198:Computer Simulation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006084:Graft Rejection / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D016040:Lung Transplantation / Q000009:adverse effects*; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats
chemical_list: C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; C546082:mirn21 microRNA, rat