Journal ArticleDOI
MicroRNA Profiling Reveals a Role for MicroRNA-218-5p in the Pathogenesis of Chronic Obstructive Pulmonary Disease
Griet Conickx,Pieter Mestdagh,Francisco Avila Cobos,Fien M. Verhamme,Tania Maes,Bart M. Vanaudenaerde,Leen J M Seys,Lies Lahousse,Richard Kim,Alan Hsu,Peter A. B. Wark,Peter A. B. Wark,Philip M. Hansbro,Guy Joos,Jo Vandesompele,Ken R. Bracke,Guy Brusselle +16 more
TLDR
In vitro and in vivo perturbation of miR‐218‐5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis and highlight a role for miR-218‐ 5p in the pathogenesis of COPD.Abstract:
Rationale: Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis.Objectives: To identify dysregulated miRNAs in lung tissue of patients with chronic obstructive pulmonary disease (COPD).Methods: We performed miRNA and mRNA profiling using high throughput stem-loop reverse-transcriptase quantitative polymerase chain reaction and mRNA microarray, respectively, on lung tissue of 30 patients (screening cohort) encompassing 8 never-smokers, 10 smokers without airflow limitation, and 12 smokers with COPD. Differential expression of miRNA-218-5p (miR-218-5p) was validated by reverse-transcriptase quantitative polymerase chain reaction in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COP...read more
Citations
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MicroRNAs: Target Recognition and Regulatory Functions
TL;DR: In this article, a review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
Journal ArticleDOI
Inflammasomes in the lung
James W. Pinkerton,Richard Kim,Avril A. B. Robertson,Jeremy A. Hirota,Lisa Wood,Darryl A. Knight,Mark E. Cooper,Luke A. J. O'Neill,Jay C. Horvat,Philip M. Hansbro +9 more
TL;DR: There is currently intense interest in the role of inflammasomes in chronic inflammatory lung diseases and in their potential for therapeutic targeting, and the known associations betweeninflammasome‐mediated responses and the development and exacerbation of chronic lung diseases are reviewed.
Journal ArticleDOI
Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma
Philip M. Hansbro,Richard Kim,Malcolm R. Starkey,Chantal Donovan,Kamal Dua,Jemma R. Mayall,Gang Liu,Nicole G. Hansbro,Jodie L. Simpson,Lisa Wood,Jeremy A. Hirota,Darryl A. Knight,Paul S. Foster,Jay C. Horvat +13 more
TL;DR: Key findings from studies are discussed where the development of representative experimental models are described to improve the understanding of the links between infection and severe, steroid‐resistant forms of this disease and how they may be applicable to obesity‐or pollution‐associated asthma.
Journal ArticleDOI
MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD.
Alan Hsu,Kamal Dua,Malcolm R. Starkey,Tatt Jhong Haw,Prema M. Nair,Kristy Nichol,Nathan W. Zammit,Shane T. Grey,Katherine J. Baines,Paul S. Foster,Philip M. Hansbro,Peter A. B. Wark,Peter A. B. Wark +12 more
TL;DR: It is found that IAV infections lead to increased inflammatory and antiviral responses in primary bronchial epithelial cells (pBECs) from healthy nonsmoking and smoking subjects and in patients with chronic obstructive pulmonary disease, and miR-125a or -b and A20 may be targeted therapeutically to inhibit excessive inflammatory responses and enhance antiviral immunity in IAV infection and in COPD.
Journal ArticleDOI
The role of cigarette smoke-induced epigenetic alterations in inflammation
TL;DR: The recognition of the molecular mechanisms of the epigenetic changes in abnormal inflammation is expected to contribute to the understanding of the pathophysiology of CS-related diseases such that novel epigenetic therapies may be identified in the near future.
References
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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian,Pablo Tamayo,Vamsi K. Mootha,Sayan Mukherjee,Benjamin L. Ebert,Michael A. Gillette,Amanda G. Paulovich,Scott L. Pomeroy,Todd R. Golub,Eric S. Lander,Jill P. Mesirov +10 more
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
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MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes
Jo Vandesompele,Katleen De Preter,Filip Pattyn,Bruce Poppe,Nadine Van Roy,Anne De Paepe,Franki Speleman +6 more
TL;DR: The normalization strategy presented here is a prerequisite for accurate RT-PCR expression profiling, which opens up the possibility of studying the biological relevance of small expression differences.
Journal ArticleDOI
MicroRNAs: Target Recognition and Regulatory Functions
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.
Journal ArticleDOI
Most mammalian mRNAs are conserved targets of microRNAs
TL;DR: This work overhauled its tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3'UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites.