KRAS mutations occur in approximately 25% of non-small cell lung cancer (NSCLC). They account for the therapy resistance to EGFR inhibitors and are suggested to be difficult to target by specific drugs. Therefore, new therapies for KRAS mutant NSCLC are urgently needed. The histone H3K4 and H3K9 di/mono-demethylase KDM1A is a key epigenetic writer, aberrantly upregulated in many cancer types, including NSCLC. In order to understand the functional role of KDM1A in the progression of lung adenocarcinoma, KDM1A expression profiles were analysed in tissue microarrays (TMAs) including 182 lung adenocarcinoma. KDM1A expression correlated with high grade and metastasized tumor. To investigate the impact of KDM1A in lung adenocarcinoma development, we used the KRAS mutated A549 cell line to establish a shRNA-mediated stable KDM1A knockdown cell clone. Unexpectedly, KDM1A knockdown had only a slight effect on retardation of cell growth. However, cell invasion and self-renewal capability was significantly decreased by KDM1A inhibition. KDM1A knockdown in A549 cell resulted in a dramatic change in the transcriptome profile as determined by RNA-Seq. Interestingly, genes involved in the KRAS signature and lung epithelial marker genes were significantly affected upon KDM1A knockdown. Ingenuity pathway analysis also suggested that the alternative integrin ß3-KRAS signaling axis, which is involved in stem cell like properties, is abrogated upon KDM1A knockdown. Indeed, Integrin ß3 and its non-canonical ligand galectin-3 were strongly downregulated and their downstream NF-?B activity was decreased upon KDM1A knockdown. Finally, correlation of KDM1A to the Integrin ß3 level was validated in TMAs. Overall design: Determining the role of KDM1A in A549 cells, mRNA profiles of control and knockdown samples of A549 cells, generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.
LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells.
Specimen part, Cell line, Subject
View SamplesPseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKOR MEF): nuclei fragmented; mitochondrial membrane potential (??mito) depolarized; Ca2+ was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca2+] (Cacyto); caspase 3/7 was activated. DKOR MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONR MEF). RNAseq analysis, qPCR and western blots showed that WT and DKOR MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), while DKONR MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONR MEF rendered them responsive to C12: ??mito depolarized, Cacyto increased and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control ??mito, Ca2+ release from the ER and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin, staurosporine but activates Bax- and Bak-independent apoptosis in response to C12. Overall design: Gene expression profiling of mouse embryo fibroblasts from WT and Bax/Bak double knock-out mice (C12 responsive and non-reponsive cell lines).
Paraoxonase 2 serves a proapopotic function in mouse and human cells in response to the Pseudomonas aeruginosa quorum-sensing molecule N-(3-Oxododecanoyl)-homoserine lactone.
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Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesTo identify liver transcripts differentially expressed due to treatment with polybrominated diphenyl ether 47 (PBDE47), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.0485, 0.485, 4.85, 48.5 or 485 mg/kg PBDE47, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesTo identify liver transcripts differentially expressed due to treatment with 1,3,5,7,9,11-hexabromocyclododecane (HBCD), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.06, 0.641, 6.41, 64.1 or 641 mg/kg HBCD, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesTo identify liver transcripts differentially expressed due to treatment with bis(2-ethylhexyl) tetrabromophthalate (TBPH), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.07, 0.71, 7.06, 70.6 or 706 mg/kg TBPH, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesTo identify liver transcripts differentially expressed due to treatment with tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-DBPE), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.1, 0.94, 9.4, 94.3 or 943 mg/kg TBBPA.DBPE, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesTo identify liver transcripts differentially expressed due to treatment with hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.05, 0.54, 5.41, 54.1 or 541 mg/kg HCDBCO, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesTo identify liver transcripts differentially expressed due to treatment with decabromodiphenyl oxide (decaBDE), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.1, 0.959, 9.59, 95.9 or 959 mg/kg decaBDE, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesTo identify liver transcripts differentially expressed due to treatment with decabromodiphenylethane (DBDPE), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.1, 0.97, 9.71, 97.1 or 970 mg/kg DBDPE, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View Samples