Identification of microRNAs in acute respiratory distress syndrome based on microRNA expression profile in rats.

Acute respiratory distress syndrome (ARDS) remains a severe disease associated with an ~40% mortality rate and as many as 200,000 new cases annually. MicroRNAs (miRNAs) have important roles in gene regulation and cancer development. The present study aimed to identify the potential roles of miRNAs in the pathogenesis and progression of ARDS. The miRNA expression profile of the GSE57223 dataset was downloaded from the Gene Expression Omnibus database. Following data normalization, differentially expressed miRNAs were identified using the t‑test method. The miRWalk database was searched to predict target genes of the identified miRNAs and then a miRNA‑miRNA network with co‑regulated target genes was constructed. Additionally, Gene Ontology (GO) analysis was performed for the target genes and a miRNA‑miRNA functional synergistic network (MFSN) was established. GO and pathway analyses were performed for the co‑regulated target genes of significant miRNAs in MFSN. Additionally, a protein‑protein‑interaction network was constructed for these target genes. A total of 19 miRNAs were differentially expressed between ARDS and normal lung tissue were identified. The four downregulated rno‑let‑7 family members were detected to have numerous co‑regulated target genes and synergistic functions. Additionally, the target genes of the four miRNAs were significantly enriched the biological processes of wounding and inflammatory response. Additionally, interleukin (IL)‑6 was identified as a hub protein with a high degree. The four downregulated rno‑let‑7 miRNAs may be involved in the inflammatory process in the pathogenesis and progression of ARDS, via the synergistic regulation of their target genes, such as IL‑6. However, additional experimental validation is required.

[1]  M. Breshears,et al.  MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome , 2014, BMC Medical Genomics.

[2]  G. Volpin,et al.  Cytokine Levels (IL-4, IL-6, IL-8 and TGFβ) as Potential Biomarkers of Systemic Inflammatory Response in Trauma Patients , 2014, International Orthopaedics.

[3]  R. Tompkins,et al.  349: INTERLEUKIN-6 PREDICTS ACUTE RESPIRATORY DISTRESS SYNDROME IN ADULTS WITH SEVERE BLUNT TRAUMA , 2013 .

[4]  S. Bellamy,et al.  The Epidemiology of Acute Respiratory Distress Syndrome in Patients Presenting to the Emergency Department With Severe Sepsis , 2013, Shock.

[5]  W. Hung,et al.  STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells , 2013, British Journal of Cancer.

[6]  Damian Szklarczyk,et al.  STRING v9.1: protein-protein interaction networks, with increased coverage and integration , 2012, Nucleic Acids Res..

[7]  J. Sznajder,et al.  Role of MicroRNAs in lung disease. , 2012, Archivos de bronconeumologia.

[8]  E. Lecuona,et al.  Rol de los microARN en las enfermedades pulmonares , 2012 .

[9]  Guangchuang Yu,et al.  clusterProfiler: an R package for comparing biological themes among gene clusters. , 2012, Omics : a journal of integrative biology.

[10]  T. Ha.  MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease , 2011, Immune network.

[11]  Dimitrios Iliopoulos,et al.  Lin28A and Lin28B Inhibit let-7 MicroRNA Biogenesis by Distinct Mechanisms , 2011, Cell.

[12]  Ankur Kulshreshtha,et al.  Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. , 2011, The Journal of allergy and clinical immunology.

[13]  Norbert Gretz,et al.  miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes , 2011, J. Biomed. Informatics.

[14]  O. Soehnlein,et al.  Contribution of Neutrophils to Acute Lung Injury , 2011, Molecular medicine.

[15]  M. Matthay,et al.  The acute respiratory distress syndrome: pathogenesis and treatment. , 2011, Annual review of pathology.

[16]  E. Olson,et al.  Pervasive roles of microRNAs in cardiovascular biology , 2011, Nature.

[17]  Yun Xiao,et al.  MiRNA–miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features , 2010, Nucleic acids research.

[18]  Kevin Struhl,et al.  STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. , 2010, Molecular cell.

[19]  C. Croce,et al.  Roles of small RNAs in tumor formation. , 2010, Trends in molecular medicine.

[20]  F. Slack,et al.  Regression of murine lung tumors by the let-7 microRNA , 2009, Oncogene.

[21]  Kevin Struhl,et al.  An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation , 2009, Cell.

[22]  D. Guidolin,et al.  miR-17 family of microRNAs controls FGF10-mediated embryonic lung epithelial branching morphogenesis through MAPK14 and STAT3 regulation of E-Cadherin distribution. , 2009, Developmental biology.

[23]  Yang Wang,et al.  Microrna-127 Modulates Fetal Lung Development , 2008 .

[24]  F. Slack,et al.  The let-7 family of microRNAs. , 2008, Trends in cell biology.

[25]  G. Mills,et al.  Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1 , 2008, Nature Genetics.

[26]  F. Slack,et al.  The let-7 microRNA reduces tumor growth in mouse models of lung cancer , 2008, Cell cycle.

[27]  E. Kistner,et al.  Let-7 expression defines two differentiation stages of cancer , 2007, Proceedings of the National Academy of Sciences.

[28]  J. Davis.  Bioinformatics and Computational Biology Solutions Using R and Bioconductor , 2007 .

[29]  E. Bargagli,et al.  Proteome analysis of bronchoalveolar lavage in lung diseases , 2006, Proteomics.

[30]  G. Petsko.  Transformation , 2006, Genome Biology.

[31]  S. Mukherjee,et al.  A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. , 2006, The New England journal of medicine.

[32]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[33]  Diane P. Martin,et al.  Incidence and outcomes of acute lung injury. , 2005, The New England journal of medicine.

[34]  Jack A. Elias,et al.  Acidic Mammalian Chitinase in Asthmatic Th2 Inflammation and IL-13 Pathway Activation , 2004, Science.

[35]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[36]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[37]  Brad T. Sherman,et al.  DAVID: Database for Annotation, Visualization, and Integrated Discovery , 2003, Genome Biology.

[38]  Edward Abraham,et al.  Neutrophils and acute lung injury , 2003, Critical care medicine.

[39]  S. Humphries,et al.  Genetic polymorphisms associated with susceptibility and outcome in ARDS. , 2002, Chest.

[40]  T. Evans,et al.  Acute respiratory distress syndrome , 1999, The Lancet.

[41]  Y. Benjamini,et al.  More powerful procedures for multiple significance testing. , 1990, Statistics in medicine.

[42]  Thomas D. Schmittgen,et al.  Integrating the MicroRNome into the study of lung disease. , 2009, American journal of respiratory and critical care medicine.

[43]  Gordon K. Smyth,et al.  limma: Linear Models for Microarray Data , 2005 .