Identification of miRNAs Potentially Involved in Bronchiolitis Obliterans Syndrome: A Computational Study

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 com...

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Bibliographic Details
Published in:PloS one 2016-08, Vol.11 (8), p.e0161771-e0161771
Main Authors: Di Carlo, Stefano, Rossi, Elena, Politano, Gianfranco, Inghilleri, Simona, Morbini, Patrizia, Calabrese, Fiorella, Benso, Alfredo, Savino, Alessandro, Cova, Emanuela, Zampieri, Davide, Meloni, Federica
Format: Article
Language:English
Subjects:
A549 Cells
Acute Disease
Algorithms
Animals
Biology and life sciences
Bronchiolitis
Bronchiolitis obliterans
Bronchiolitis Obliterans - genetics
Bronchopneumonia
Chronic Disease
Computation
Computer applications
Computer Simulation
Development and progression
Disease
Epigenesis, Genetic
Epigenetics
Experiments
Filtration
Gene expression
Gene Expression Regulation
Gene Regulatory Networks
Genetic aspects
Graft rejection
Graft Rejection - pathology
Humans
In Situ Hybridization
Lung cancer
Lung transplantation
Lung Transplantation - adverse effects
Lungs
Medicine and Health Sciences
MicroRNA
MicroRNAs
MicroRNAs - genetics
miRNA
Pathogenesis
Physiological aspects
Pipelines
Pulmonary fibrosis
Rats
Respiratory diseases
Signal transduction
Statistical analysis
Thoracic surgery
Transplants & implants
Xenografts
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0161771