title: MicroRNAs Implicated in Dysregulation of Gene Expression Following Human Lung Transplantation.
abstract: BACKGROUND
  Lung transplantation remains the only viable treatment option for the majority of patients with advanced lung diseases. However, 5-year post-transplant survival rates remain low primarily secondary to chronic rejection. Novel insights from global gene expression profiles may provide molecular phenotypes and therapeutic targets to improve outcomes after lung transplantation.
  
  
  METHODS
  Whole-genome gene expression profiling was performed in a cohort of patients that underwent lung transplantation as well as healthy controls using the Affymetrix Human Exon 1.0ST Array. To explore the potential roles of microRNAs (miRNAs) in regulating lung transplantation-associated gene dysregulation, miRNA expression levels were also profiled in the same samples using the Exiqon miRCURY(™) LNA Array.
  
  
  RESULTS
  In a cohort of 18 lung transplant patients, 364 dysregulated genes were identified in Caucasian lung transplant patients relative to normal individuals. Pathway enrichment analysis of the dysregulated genes pointed to Gene Ontology biological processes such as "defense response", "immune response" and "response to wounding". We then compared the expression profiles of potential regulating miRNAs, suggesting that dysregulation of a number of lung transplantation-associated genes (e.g., ATR, FUT8, LRRC8B, NFKBIA) may be attributed to the dysregulation of their respective regulating miRNAs.
  
  
  CONCLUSIONS
  Following human lung transplantation, a substantial proportion of genes, particularly those genes involved in certain biological processes like immune response, were dysregulated in patients relative to their healthy counterparts. This exploratory analysis of the relationships between miRNAs and their gene targets in the context of lung transplantation warrants further investigation and may serve as novel therapeutic targets in lung transplant complications.
authors.affiliation: Department of Pediatrics, University of Illinois, Chicago, IL 60612 ; Institute of Human Genetics, University of Illinois, Chicago, IL 60612.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, IL 60612 ; Section of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Section of Pulmonary/Critical Care, Department of Medicine, University of Chicago, Chicago, IL 60637.
authors.forename: Shwu-Fan
authors.initials: SF
authors.lastname: Ma
authors.affiliation: Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, IL 60612 ; Section of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Machado
authors.affiliation: Section of Pulmonary/Critical Care, Department of Medicine, University of Chicago, Chicago, IL 60637.
authors.forename: Sangeeta M
authors.initials: SM
authors.lastname: Bhorade
authors.affiliation: Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, IL 60612 ; Section of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
keywords: gene expression; gene ontology; lung transplant; microRNA; pathway