Gene expression data of Kas-/- mouse emobryonic fibroblasts transfected with KRAS siRNAs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59823 | GEO | 2014/09/01
SECONDARY ACCESSION(S): PRJNA256309
REPOSITORIES: GEO
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Project description:We used Kras/Hras/Nras-triple knockout MEFs expressing recombinant Nras to test the off-target effect of 2 Kras siRNAs at different transfection concentrations. Gene expression profiles were generated using Affimymetrix Mouse Gene ST 2.0 microarrays. Cells were transfected with Kras siRNAs and gene expression profiles were generated to identify genes up or down regulated by each siRNA at different transfection concentrations.
2014-09-01 | E-GEOD-59823 | biostudies-arrayexpress
Project description:Mutations of the proto-oncogene KRas, together with the inactivation of the onco-suppressor genes APC and TP53, are considered to have an important role both in the carcinogenesis and in the colorectal tumor progression. The oncogene K-ras has activating mutations, especially in codon 12, in about 40% to 50% of colorectal carcinomas (Andreyev et al., 1998). The mechanism by which oncogenic K-ras alone contribuites to tumor progression in colon cancer is largely unknown. To this end, we have developed a model system where the colorectal adenocarcinoma cell line Colo741 has been stably trasfected with the Kras-G12V or Kras-G12D mutated oncogenes. Our results demonstrate how expression profiling data can be used to interpret changes in cellular characteristics induced by transfection and hence provide some clues as to the mechanisms by which different activated K-Ras impair processes mediated by endogenous wild-type KRas proteins. We made for the production of cell clones that could be utilized as useful in vitro models. The adenocarcinoma cell line Colo741 has been chosen to produce stable transfectants for two mutant forms of KRas2 (Gly12Val and Gly12Asp) and the wild-type coding sequence (as experiment control). After the transfection, the cells have been selected (with G418), cloned (by limited dilutions) and screened (by RT-PCR). The total RNAs, Dnase-treated, from five cell clones per condition, have been pooled. The samples, constituted by biotin-labeled cRNA, derived from a pool of five cell clones obtained from transfection of the adenocarcinoma cell line Colo741 with either pcDNA3.1-KRas2(Wt) or pcDNA3.1-KRas2(Gly12Val) or pcDNA3.1KRas2(Gly12Asp). They were hybridized to a Human Gene 1.0 ST array (Affymetrix). Two technical replicates have been performed for each condition.
2008-12-17 | E-GEOD-12398 | biostudies-arrayexpress
Project description:KRAS is the most frequently mutated oncogene in human cancers, but to date, only KRASG12C inhibitors have been FDA-approved. Small-molecule inhibitors that target other more prevalent KRAS mutations are in urgent clinical need. Here, we report a highly potent pan-KRAS inhibitor, MCB-294, that selectively targets KRAS, but not HRAS or NRAS. Molecular profiling studies show that MCB-294 binds to and inhibits several KRAS mutants, including G12D, G12C, G12V, thereby disabling KRAS oncogenic signaling. MCB-294 is well tolerated in mice and exhibits remarkable therapeutic efficacy against the growth of a comprehensive range of KRAS-driven cancer cell lines, patient-derived organoids, and tumor xenografts and prolongs mouse survival. By employing an MCB-294 derivative as the KRAS binder, we further identify a VHL-based pan-KRAS degrader, MCB-36, that efficiently degrades KRAS in vitro and in vivo through the ubiquitin-proteasome system. Importantly, MCB-294 and MCB-36 not only effectively kill KRASG12C inhibitor-resistant cells, but also reshape the tumor microenvironment by boosting T cell-mediated anti-tumor immunity. Taken together, our findings demonstrate a successful and feasible strategy for targeting pan-KRAS to impair multifaceted features of KRAS-driven cancers.
2024-08-03 | GSE273300 | GEO
Project description:KRAS is the most frequently mutated oncogene in human cancers, but to date, only KRASG12C inhibitors have been FDA-approved. Small-molecule inhibitors that target other more prevalent KRAS mutations are in urgent clinical need. Here, we report a highly potent pan-KRAS inhibitor, MCB-294, that selectively targets KRAS, but not HRAS or NRAS. Molecular profiling studies show that MCB-294 binds to and inhibits several KRAS mutants, including G12D, G12C, G12V, thereby disabling KRAS oncogenic signaling. MCB-294 is well tolerated in mice and exhibits remarkable therapeutic efficacy against the growth of a comprehensive range of KRAS-driven cancer cell lines, patient-derived organoids, and tumor xenografts and prolongs mouse survival. By employing an MCB-294 derivative as the KRAS binder, we further identify a VHL-based pan-KRAS degrader, MCB-36, that efficiently degrades KRAS in vitro and in vivo through the ubiquitin-proteasome system. Importantly, MCB-294 and MCB-36 not only effectively kill KRASG12C inhibitor-resistant cells, but also reshape the tumor microenvironment by boosting T cell-mediated anti-tumor immunity. Taken together, our findings demonstrate a successful and feasible strategy for targeting pan-KRAS to impair multifaceted features of KRAS-driven cancers.
2024-07-30 | GSE273116 | GEO
Project description:KRAS is the most frequently mutated oncogene in human cancers, but to date, only KRASG12C inhibitors have been FDA-approved. Small-molecule inhibitors that target other more prevalent KRAS mutations are in urgent clinical need. Here, we report a highly potent pan-KRAS inhibitor, MCB-294, that selectively targets KRAS, but not HRAS or NRAS. Molecular profiling studies show that MCB-294 binds to and inhibits several KRAS mutants, including G12D, G12C, G12V, thereby disabling KRAS oncogenic signaling. MCB-294 is well tolerated in mice and exhibits remarkable therapeutic efficacy against the growth of a comprehensive range of KRAS-driven cancer cell lines, patient-derived organoids, and tumor xenografts and prolongs mouse survival. By employing an MCB-294 derivative as the KRAS binder, we further identify a VHL-based pan-KRAS degrader, MCB-36, that efficiently degrades KRAS in vitro and in vivo through the ubiquitin-proteasome system. Importantly, MCB-294 and MCB-36 not only effectively kill KRASG12C inhibitor-resistant cells, but also reshape the tumor microenvironment by boosting T cell-mediated anti-tumor immunity. Taken together, our findings demonstrate a successful and feasible strategy for targeting pan-KRAS to impair multifaceted features of KRAS-driven cancers.
2024-08-03 | GSE273301 | GEO
Project description:Mutations in the NRAS oncogene are present in up to 20% of melanoma. Here, we show that interferon alpha-inducible protein 6 (IFI6) is necessary for NRASQ61K-induced transformation and melanoma growth. IFI6 was transcriptionally upregulated by NRASQ61K, and knockdown of IFI6 resulted in DNA replication stress due to dysregulated DNA replication via E2F2. This stress consequentially inhibited cellular transformation and melanoma growth via senescence or apoptosis induction depending on the RB and p53 pathway status of the cells. NRAS-mutant melanoma were significantly more resistant to the cytotoxic effects of DNA replication stress-inducing drugs, and knockdown of IFI6 increased sensitivity to these drugs. Pharmacological inhibition of IFI6 expression by the MEK inhibitor trametinib, when combined with DNA replication stress-inducing drugs, blocked NRAS-mutant melanoma growth. Collectively, we demonstrate that IFI6, via E2F2 regulates DNA replication and melanoma development and growth, and this pathway can be pharmacologically targeted to inhibit NRAS-mutant melanoma. MEL-ST cells expressing either empty vector or mutant oncogenic RAS genes (HRAS v12, KRAS v12, NRAS Q61K) were used to isolate total RNA. The RNA was then used to perform gene expression analyses using the Illumina HumanHT-12 V4.0 Expression BeadChip array.
2016-09-08 | E-GEOD-62827 | biostudies-arrayexpress
Project description:Mutations of the proto-oncogene KRas, together with the inactivation of the onco-suppressor genes APC and TP53, are considered to have an important role both in the carcinogenesis and in the colorectal tumor progression. The oncogene K-ras has activating mutations, especially in codon 12, in about 40% to 50% of colorectal carcinomas (Andreyev et al., 1998). The mechanism by which oncogenic K-ras alone contribuites to tumor progression in colon cancer is largely unknown. To this end, we have developed a model system where the colorectal adenocarcinoma cell line Colo741 has been stably trasfected with the Kras-G12V or Kras-G12D mutated oncogenes. Our results demonstrate how expression profiling data can be used to interpret changes in cellular characteristics induced by transfection and hence provide some clues as to the mechanisms by which different activated K-Ras impair processes mediated by endogenous wild-type KRas proteins.
2008-12-18 | GSE12398 | GEO
Project description:We investigated a comprehensive and quantitative interactome of RAS, a protein found to be a driver of many human cancers. This resource identifies interactors of the active form of RAS (nucleotide-dependent) as well as isoform-specific (KRAS, HRAS, and NRAS) interactors of RAS. Several of the proteins identified were confirmed as being important for cancer cell viability and senescence.
2022-10-13 | PXD034847 | Pride
Project description:To identify the gene expression changes in NRAS mutant cell line SKMEL-103, KRAS mutant cell line AsPC1 and HRAS mutant cell line RH-36 upon BAY 11-7082 treatment, we analyzed these cell line with either control DMSO or BAY 11-7082 treatment via RNA sequencing.
2024-08-08 | GSE251968 | GEO
Project description:We determined the specific protein interactomes of each RAS isoform (HRAS G12V, NRAS G12V and KRAS G12V) by BirA proximity-dependent biotin identification (BioID) in HEK-HT cells (folder hnk ras). We also determined protein interactomes of KRASG12V (folder: ras1) and HRASG12V (folder: ras2) in PIP5K1A deficient HEK-HT cells.
2018-07-08 | MSV000082583 | MassIVE