Purpose: Identify whole lung gene expression patterns in a house dust mite model of mild/moderate asthma Methods: Lung gene expression profiles of 10 week old BALB/c female mice were generated by ribosome-depleted, 150 nt, paired-end, stranded RNA-seq with Illumina HiSeq v4. Sequence reads that passed quality filters after trimming were analyzed with Sailfish-cir to identify linear RNAs and circular RNAs. Differential expression of linear RNAs was assessed with Deseq2 . QRT–PCR validation was performed using TaqMan and SYBR Green methods. Results: 100 million sequence reads per sample were mapped to the mouse genome (build mm10) using Sailfish-cir to identify linear and circular RNA transcripts. Pathway analysis of differentially expressed genes identified upregulation of gene sets for human asthma, mouse lung allergic inflammation, Muc5ac regulated genes and smooth muscle genes after allergic sensitization. Gene level exppression in each asthma-related pathway was reduced by the miR-145 antagonist. The miR-145 antagonist and several nontargeting oligos also upregulated interferon signaling pathways suggesting a general antiinflammatory effect of LNA/DNA oligos in the lung. Conclusions: Lung-directed delivery of LNA/DNA oligonucleotides with cationic lipid nanoparticles is an efffective means to prevent inflammatory gene expression in a house dust mite model of mild/moderate asthma. Overall design: Linear and circular RNA transcript expression was compared in whole lung tissue from unsensitized, house dust mite sensitzed, antimiR-145 treated treated mice
Nanoparticle Delivery of Anti-inflammatory LNA Oligonucleotides Prevents Airway Inflammation in a HDM Model of Asthma.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesPurpose: Identify whole lung gene expression patterns modified by nanoparticle delivery of an antisense LNA/DNA oligonucleotide targeting mmu-miR145a-5p and nontargeting oligonucleotides Methods: Lung gene expression profiles of 10 week old BALB/c female mice were generated by polyA RNA-seq with Illumina HiSeq v4. Sequence reads that passed quality filters after timming were analyzed at the gene level with RNA STAR, featureCounts and Deseq2 . qRT–PCR validation was performed using TaqMan and SYBR Green methods. Results: 10-15 million sequence reads per sample were mapped to the mouse genome (build mm10). Pathway analysis of differentially expressed genes identified upregulation of gene sets for human asthma, mouse lung allergic inflammation, Muc5ac regulated genes and smooth muscle genes after allergic sensitization. Gene level exppression in each asthma-related pathway was reduced by the miR-145 antagonist. The miR-145 antagonist and several nontargeting oligos also upregulated interferon signaling pathways suggesting a general antiinflammatory effect of LNA/DNA oligos in the lung. Conclusions: Lung-directed delivery of LNA/DNA oligonucleotides with cationic lipid nanoparticles is an efffective means to prevent inflammatory gene expression in a house dust mite model of asthma Overall design: Lung gene expression in unsensitized, house dust mite sensitized, antimiR-145 treated and nontargeting oligonucleotide treated mice
Nanoparticle Delivery of Anti-inflammatory LNA Oligonucleotides Prevents Airway Inflammation in a HDM Model of Asthma.
Age, Specimen part, Cell line, Subject
View SamplesThis was a collaborative study to discover somatic mutations in 188 lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are likely to play a role in carcinogenesis. The observed mutational profiles correlate with clinical features, smoking status, and DNA repair defects. These results are complemented by data integration including SNP array data and gene expression array data (deposited here). Our findings shed further light on several key signaling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
Somatic mutations affect key pathways in lung adenocarcinoma.
Sex, Race
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