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GSE145677
Homo sapiens
6 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Human Exon 1.0 ST Array (huex10st)
Description
Senataxin (SETX) is an RNA/DNA helicase that has been implicated in transcriptional regulation and the DNA damage response, through resolution of R-loop structures. Mutations in SETX result in either of two distinct neurodegenerative disorders. SETX dominant mutations result in a juvenile form of ALS (amyotrophic lateral sclerosis) named ALS4, while recessive mutations are responsible for an ataxia called AOA2 (ataxia with oculomotor apraxia type 2). How mutations in the same protein can lead to different phenotypes is still unclear. To elucidate AOA2 disease mechanisms, we first examined gene expression changes following SETX depletion. We observed effects on both transcription and RNA processing, but surprisingly observed decreased R-loop accumulation in SETX depleted cells. Importantly, we discovered a strong connection between SETX and the autophagy pathway, reflecting a direct effect on the transcription of autophagy genes. We show that SETX depletion inhibits the progression of autophagy, leading to an accumulation of ubiquitinated proteins, decreased ability to clear protein aggregates, as well as mitochondrial defects. Analysis of AOA2 patient fibroblasts also revealed a perturbation of the autophagy pathway. Our work has thus identified a novel function for SETX in the regulation of autophagy, whose modulation may have a therapeutic impact for AOA2.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Polyadenylation of mRNA precursors is mediated by a large multisubunit protein complex. Here we show that RBBP6 (retinoblastoma-binding protein 6), identified initially as an Rb- and p53-binding protein, is a component of this complex and functions in 3' processing in vitro and in vivo. RBBP6 associates with other core factors, and this interaction is mediated by an unusual ubiquitin-like domain, DWNN (domain with no name), that is required for 3' processing activity. The DWNN is also expressed, via alternative RNA processing, as a small single-domain protein (isoform 3 [iso3]). Importantly, we show that iso3, known to be down-regulated in several cancers, competes with RBBP6 for binding to the core machinery, thereby inhibiting 3' processing. Genome-wide analyses following RBBP6 knockdown revealed decreased transcript levels, especially of mRNAs with AU-rich 3' untranslated regions (UTRs) such as c-Fos and c-Jun, and increased usage of distal poly(A) sites. Our results implicate RBBP6 and iso3 as novel regulators of 3' processing, especially of RNAs with AU-rich 3' UTRs.
Publication Title
RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3' UTRs.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 398 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The analytical validation of a 15 gene prognostic signature for early-stage, completely resected, non-small-cell lung carcinoma that distinguishes between patients with good and poor prognoses.
Publication Title
Analytical Performance of a 15-Gene Prognostic Assay for Early-Stage Non-Small-Cell Lung Carcinoma Using RNA-Stabilized Tissue.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 219 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Race, Time
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 62 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Rosiglitazone, a peroxisome proliferator-activated receptor g (PPARg) agonist of the thiazolidinedione class, is a major insulin-sensitizing drug widely used to treat type-2 diabetes. Rosiglitazone causes myocardial hypertrophy in rodents and increases the risk of cardiac events in man. To better characterize its cardiac effects, male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone.
Publication Title
No associated publication
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
miR-155 is a microRNA associated with poor prognosis in lymphoma and leukemia and has been implicated in the progression of Mycosis Fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). In this study, we developed and tested Cobomarsen (MRG-106), a locked nucleic acid-modified oligonucleotide inhibitor of miR-155. In MF cell lines in vitro, inhibition of miR-155 with Cobomarsen de-repressed direct miR-155 targets, decreased expression of multiple gene pathways associated with cell survival, reduced survival signaling, decreased cell proliferation, and activated apoptosis.
Publication Title
Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Sex, Disease, Cell line, Race, Time
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Sex, Specimen part, Cell line, Race
View Samples