Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA360820 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A subtype of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like (ABC) DLBCL, depends on constitutive NF-kB pathway signaling for survival. Small molecule inhibitors of IkB kinase b (IKKb), a key regulator of the NF-kB pathway, kill ABC DLBCL cells and hold promise for the treatment of this lymphoma type. We conducted an RNA interference genetic screen to investigate potential mechanisms of resistance of ABC DLBCL cells to IKKb inhibitors. We screened a library of small hairpin RNAs (shRNAs) targeting 500 protein kinases for shRNAs that would kill an ABC DLBCL cell line in the presence of a small molecule IKKb inhibitor more effectively than in its absence. Two independent shRNAs targeting IKKa synergized with the IKKb inhibitor to kill three different ABC DLBCL cell lines but were not toxic by themselves. Surprisingly, IKKa shRNAs blocked the classical rather than the alternative NF-kB pathway in ABC DLBCL cells, as judged by inhibition of IkBa phosphorylation. IKKa shRNA toxicity was reversed by coexpression of wild type but not kinase inactive forms of IKKa, suggesting that IKKa may directly phosphorylate IkBa under conditions of IKKb inhibition. These results suggest that therapy for ABC DLBCL may be improved by targeting both IKKa and IKKb. Keywords: compound treatment design Gene expression profiling of OCI-Ly3 cells with or without expressing IKKa shRNA in the presence or absence of 12.5 uM IKKb inhibitor for 2 and 3 days. Four samples were analyzed.
2009-06-01 | E-GEOD-11902 | biostudies-arrayexpress
Project description:A subtype of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like (ABC) DLBCL, depends on constitutive NF-kB pathway signaling for survival. Small molecule inhibitors of IkB kinase b (IKKb), a key regulator of the NF-kB pathway, kill ABC DLBCL cells and hold promise for the treatment of this lymphoma type. We conducted an RNA interference genetic screen to investigate potential mechanisms of resistance of ABC DLBCL cells to IKKb inhibitors. We screened a library of small hairpin RNAs (shRNAs) targeting 500 protein kinases for shRNAs that would kill an ABC DLBCL cell line in the presence of a small molecule IKKb inhibitor more effectively than in its absence. Two independent shRNAs targeting IKKa synergized with the IKKb inhibitor to kill three different ABC DLBCL cell lines but were not toxic by themselves. Surprisingly, IKKa shRNAs blocked the classical rather than the alternative NF-kB pathway in ABC DLBCL cells, as judged by inhibition of IkBa phosphorylation. IKKa shRNA toxicity was reversed by coexpression of wild type but not kinase inactive forms of IKKa, suggesting that IKKa may directly phosphorylate IkBa under conditions of IKKb inhibition. These results suggest that therapy for ABC DLBCL may be improved by targeting both IKKa and IKKb. Keywords: compound treatment design
2009-06-01 | GSE11902 | GEO
Project description:Comparison of wild type mouse colon carcinoma cancer cell lines to transfected cell lines with Kras sh RNA
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Project description:Comparison of gene expression of lung tissues between WT, IKKa floxed, Kras, and Kras;IKKa floxed mice
2016-12-31 | GSE84159 | GEO
Project description:Comparison of gene expression of mouse lung adenocarcinoma-associated macrophages isolated from C57BL/6 mice injected with Kras-CL and Kras IKKa low cells
2018-05-16 | GSE114501 | GEO
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2019-03-01 | GSE122419 | GEO
Project description:Comparison of wild type mouse lung cancer cell lines to transfected cell lines with Spp1 sh RNA
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Project description:Comparison of wild type mouse lung cancer cell lines to transfected cell lines with Nras sh RNA
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Project description:We report the results of scRNA sequencing of parental and mIDH2R140Q TF-1 cell lines following exposure to PBS (control) and IL-1B. We obtained 1 million cells of each cell line for each condition and incubated them with either PBS or IL-1B. Following treatment, cells were processed using previously described inDrop protocols (Wolock et al., 2019 Cell Reports). Samples were split into 3,000 single-cell transcriptomes and one library per sample was prepared and sequenced on NextSeq 500. Data was prepared for analysis as described in our methods and gene expression was normalized and quantified. Gene set enrichment, differential gene expression and UMAP visualization was performe dusing SEurat 3.0. Ultimately, we compared the cellular response of parental and mIDH2 cells to IL-1B and our results indicate that mIDH2 cells have augmented expression of NF-κB target transcripts . This component of our study demonstrates a dynamic response of both cell lines to IL-1B with an exaggerated response seen in mIDH2 cells.
2021-11-05 | GSE187777 | GEO
Project description:Compensatory IKKa activation of classical NF-kB signaling during IKKb inhibition
| PRJNA105739 | ENA