Expression data from Sos1 and Sos2-depleted (individually or combined) mouse primary fibroblasts
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PROVIDER: PRJNA1162542 | ENA |
REPOSITORIES: ENA
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Project description:Sos1 and Sos2 are guanine-nucleotide exchange factors for Ras and Rac small GTPases, which are involved in a wide range of cellular responses including proliferation and migration. We have previously shown that Sos1 and Sos2 have different effects on cell migration, but the underlying mechanisms are not clear. Here, we examined the role of Sos1 and Sos2 in the overall transcriptional profile of mouse primary fibroblasts in order to unveil the specific functions of these Ras/Rac activators in regulating migration. We used microarrays to detail the impact of Sos1/2 depletion (individual or combined) in the transcriptional signature of mouse primary keratinocytes
2024-09-23 | GSE277505 | GEO
Project description:Sos proteins are involved in the maintaining of skin homeostasis and participate in the initiation/progression of chemically-induced skin cancer. However, the precise role of these proteins in specific skin cellular compartments remains undetermined. Here, we examined the role of Sos1 and Sos2 in the overall transcriptional profile of mouse primary keratinocytes in order to unveil the specific functions of these Ras activators in keratinocyte population. We used microarrays to detail the impact of Sos1/2 depletion (individual or combined) in the transcriptional signature of mouse primary keratinocytes
2021-02-03 | GSE166020 | GEO
Project description:Expression data from Sos1 and Sos2-depleted (individally or combined) mouse primary keratinocytes
| PRJNA698993 | ENA
Project description:Emerging evidence suggests Jumonji domain-containing proteins are epigenetic regulators in diverse biological processes including cellular differentiation and proliferation. RNA interference-based analyses combined with gene expression profiling can effectively characterize the cellular functions of these enzymes. We found that the depletion of Jumonji domain-containing protein 6 (Jmjd6) and its paralog protein Jumonji domain-containing protein 4 (Jmjd4) individually by small hairpin RNAs (shRNAs) slowed cell proliferation of mouse NIH3T3 fibroblasts. We subsequently performed gene expression profiling on both Jmjd6- and Jmjd4-depleted mouse NIH3T3 fibroblasts using the Affymetrix GeneChip Mouse Exon 1.0 ST Array. We anaylzed control shRNA-treated cells, Jmjd6- and Jmjd4- depleted cells using Affymetrix Mouse Exon 1.0 ST platform. Two biological replicates were performed (total 6 samples). Array data was processed by Affymetrix Expression Console.
2016-01-12 | E-GEOD-76758 | biostudies-arrayexpress
Project description:Emerging evidence suggests Jumonji domain-containing proteins are epigenetic regulators in diverse biological processes including cellular differentiation and proliferation. RNA interference-based analyses combined with gene expression profiling can effectively characterize the cellular functions of these enzymes. We found that the depletion of Jumonji domain-containing protein 6 (Jmjd6) and its paralog protein Jumonji domain-containing protein 4 (Jmjd4) individually by small hairpin RNAs (shRNAs) slowed cell proliferation of mouse NIH3T3 fibroblasts. We subsequently performed gene expression profiling on both Jmjd6- and Jmjd4-depleted mouse NIH3T3 fibroblasts using the Affymetrix GeneChip Mouse Exon 1.0 ST Array.
2016-01-12 | GSE76758 | GEO
Project description:KRAS is the most frequently mutated driver of pancreatic, colorectal, and non-small cell lung cancers. Direct KRAS blockade has proven challenging and inhibition of a key downstream effector pathway, the RAF-MEK-ERK cascade, has shown limited success due to activation of feedback networks that keep the pathway in check. We hypothesized that inhibiting SOS1, a KRAS activator and important feedback node, represents an effective approach to treat KRAS-driven cancers. We report the discovery of a highly potent, selective and orally bioavailable small-molecule SOS1 inhibitor, BI-3406, that binds to the catalytic domain of SOS1 thereby preventing the interaction with KRAS. BI-3406 reduces formation of GTP-loaded RAS and limits cellular proliferation of a broad range of KRAS-driven cancers. Importantly, BI-3406 attenuates feedback reactivation induced by MEK inhibitors and thereby enhances sensitivity of KRAS-dependent cancers to MEK inhibition. Combined SOS1 and MEK inhibition represents a novel and effective therapeutic concept to address KRAS-driven tumors.
2020-08-20 | GSE128385 | GEO
Project description:Expression profiling of androgen and insulin pathway regulating genes unveils SOS 1 as candidate gene for idiopathic hirsutism Background: Idiopathic Hirsutism (IH), defined as the presence of terminal hairs in females in a male-like pattern, affecting about 5% -15% of women, may result from the interaction between the androgen level and the sensitivity of the hair follicle to the androgen. The pathophysiology of IH is presumed to be linked to increased SRD5A activity, probably both isoenzyme types (SRD5A1 and SRD5A2) and generally related to an alteration in androgen receptor (AR) function. IH is often associated to metabolic syndrome, visceral obesity, dyslipidemia, insulin resistance, and hypertension.Methodology/Principal Findings: With the aim of identifying genes involved in the pathogenesis of this disorder, we investigated the expression profile of 190 genes involved in the androgen biosynthesis and metabolism, and other genes coding for products active in the insulin pathway in skin genital fibroblasts. For this purpose we selected from a cohort of 240 women affected with androgen excess syndrome a group of 52 idiopathic hirsute patients (22%) and we selected 8 of them with the higher grade of hirsutism (Ferriman & Gallway score >20) for the genetic studies comparing the data with 4 healthy women used as controls. The array gene signature in the IH patients identified 4 differentially expressed genes, 2 up-regulated and 2 down-regulated (FC≥± 1.5). Differentially expressed genes included products involved in insulin signalling while no androgens related genes were found altered in expression levels. We found that one of the over expressed transcript codes for the SOS1 gene product, which is overproduced in IH patients compared to controls. We did not identified any genomic variants or SNPs in the SOS1 promoter region and/or witin the 3’UTR with documented functional effects on SOS1 gene expression, although some variants in the 3’UTR seems to be potentially active in modulating the binding of transcription factors. Conclusions/Significance: In the cohort of women with androgen excess syndrome studied the 22% had neither hyperandrogenemia nor biochemical sign of hyperinsulinemia. We were able to demonstrate that SOS1 mRNA is over-expressed resulting in over production of SOS1 protein in IH patients. This suggests that an increase of SOS1 protein production could reflect a situation with an increased SOS1 activity function in hirsute patients. These findings propose a role for SOS1, in cooperation with other insulin pathway genes, in the pathogenesis of IH.
2010-04-15 | GSE18022 | GEO
Project description:We performed RNA-seq experiments on three biological replicates of HeLa cells depleted of MATR3, PTBP1/2, controls, or combined depletion of MATR3/PTBP1/2. Cells were fractionated into cytoplasmic and nuclear RNA. Library preparation was done with the TruSeq stranded RNAseq library kit (Illumina) according to manufacturer’s recommendations; RNA was depleted of rRNA using the RiboZero kit (Epicentre). All libraries were sequenced on Illumina HiSeq2 machines in a single-end manner with a read length of 100 nt.
2018-05-01 | E-MTAB-6204 | biostudies-arrayexpress
Project description:Genome-wide transcriptional profiles of parental and mtDNA-depleted mouse embryonic fibroblasts. Analysis revealed a downregulation of ChrM genes.
2014-11-03 | GSE59972 | GEO
Project description:KRAS inhibitors have demonstrated exciting pre-clinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KRASG12D, p53 mutant, murine PDAC-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy. Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intra-tumoral CD8+ T cells without durable responses. scRNA-sequencing revealed an increase in inflammatory cancer associated fibroblasts (iCAFs), M2 macrophages, and a decreased dendritic cell quality that ultimately resulted in a highly immunosuppressive microenvironment driven by IL6+ iCAFs. Agonist CD40 treatment was effective to revert macrophage polarization and overcome the lack of mature antigen presenting DCs after SOS1i+MEKi therapy. Treatment increased the overall survival of KPCY tumor-bearing mice. The addition of checkpoint blockade to SOS1i+MEKi combination resulted in tumor free mice with established immune memory. Our data suggests that KRAS inhibition affects myeloid cell maturation and highlights the need for combining KRAS cancer-targeted therapy with myeloid activation to enhance and prolong anti-tumor effects.
2024-04-22 | GSE264527 | GEO