Effect of depletion of FUS on gene expression during in sunitinib-resistance cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE226245 | GEO | 2023/03/31
REPOSITORIES: GEO
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2021-11-03 | PXD027065 | Pride
Project description:Sunitinib is a TKI inhibitor used for managing metastatic renal cell carcinoma (RCC). However, chronic sunitinib treatment in RCC usually results in the development of drug resistance via alternating phosphorylation dynamics. On the other hand, 17-beta-estradiol, or estrogen, has been demonstrated to repress RCC growth partly through regulating cell signallings. To investigate how estrogen can repress sunibitinib-resistant RCC growth and its the possible mechanism of action related protein phosphorylation, a label-free quantitative phosphoproteomics study is performed.
2020-08-07 | PXD011020 | Pride
Project description:The clinical response to sunitinib in advanced renal-cell carcinoma (RCC) is frequently limited in magnitude and duration due to drug resistance, but the underlying mechanisms remain elusive. To discover mechanisms of resistance, we developed drug-resistant cell lines and have their gene expressions profiled and compared. Results provide insight into the molecular mechanisms underlying sunitinib-resistance.
2016-09-30 | GSE69535 | GEO
Project description:The tyrosine kinase inhibitor sunitinib is an effective first-line treatment for patients with advanced renal cell carcinoma (RCC). Hypothesizing that a functional read-out by mass spectrometry-based (phospho, p-)proteomics will identify predictive biomarkers for treatment outcome of sunitinib, tumor tissues of 26 RCC patients were analyzed. Eight patients were primary resistant (RES) and 18 sensitive (SENS).
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Project description:FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNA, but its role at the synapse is poorly understood. Here, we used super-resolution imaging to determine the physiological localization of extranuclear, neuronal FUS and found it predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosome preparations, we identified synaptic RNA targets of FUS that are associated with synapse organization and plasticity. Synaptic FUS was significantly increased in a knock-in mouse model of ALS-FUS, at presymptomatic stages. Despite apparently unaltered synaptic organization, RNA-seq of synaptoneurosomes highlighted age-dependent dysregulation of glutamatergic and GABAergic synapses. Our study indicates that FUS relocalization to the synapse in early stages of ALS-FUS results in synaptic impairment, potentially representing an initial trigger of neurodegeneration.
2021-03-05 | E-MTAB-9211 | biostudies-arrayexpress
Project description:FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNA, but its role at the synapse is poorly understood. Here, we used super-resolution imaging to determine the physiological localization of extranuclear, neuronal FUS and found it predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosome preparations, we identified synaptic RNA targets of FUS that are associated with synapse organization and plasticity. Synaptic FUS was significantly increased in a knock-in mouse model of ALS-FUS, at presymptomatic stages. Despite apparently unaltered synaptic organization, RNA-seq of synaptoneurosomes highlighted age-dependent dysregulation of glutamatergic and GABAergic synapses. Our study indicates that FUS relocalization to the synapse in early stages of ALS-FUS results in synaptic impairment, potentially representing an initial trigger of neurodegeneration.
2021-03-05 | E-MTAB-9212 | biostudies-arrayexpress
Project description:FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNA, but its role at the synapse is poorly understood. Here, we used super-resolution imaging to determine the physiological localization of extranuclear, neuronal FUS and found it predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosome preparations, we identified synaptic RNA targets of FUS that are associated with synapse organization and plasticity. Synaptic FUS was significantly increased in a knock-in mouse model of ALS-FUS, at presymptomatic stages. Despite apparently unaltered synaptic organization, RNA-seq of synaptoneurosomes highlighted age-dependent dysregulation of glutamatergic and GABAergic synapses. Our study indicates that FUS relocalization to the synapse in early stages of ALS-FUS results in synaptic impairment, potentially representing an initial trigger of neurodegeneration.
2021-03-05 | E-MTAB-10104 | biostudies-arrayexpress
Project description:To gain insights into the mechanisms of dihydroberberine, sunitinib and dihydroberberine plus sunitinib on inhibition to A549 cells, we have employed whole genome microarray expression profiling as a discovery platform to identify different genes between dihydroberberine, sunitinib and dihydroberberine plus sunitinib-treated sample and control.
2015-06-26 | GSE70282 | GEO
Project description:FUS is an RNA-binding protein involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS-containing aggregates are often associated with concomitant loss of nuclear FUS. Whether loss of nuclear FUS function, gain of a cytoplasmic function, or a combination of both lead to neurodegeneration remains elusive. To address this question, we generated knock-in mice expressing mislocalized cytoplasmic FUS and complete FUS knock-out mice. Both mouse models display similar perinatal lethality with respiratory insufficiency, reduced body weight and length, and largely similar alterations in gene expression and mRNA splicing patterns, indicating that mislocalized FUS results in loss of its normal function. However, FUS knock-in mice, but not FUS knock-out mice, display reduced motor neuron numbers at birth, associated with enhanced motor neuron apoptosis, which can be rescued by cell-specific CRE-mediated expression of wild-type FUS within motor neurons. Together, our findings indicate that cytoplasmic FUS mislocalization not only leads to nuclear loss of function, but also triggers motor neuron death through a toxic gain of function within motor neurons. Total RNA from brains of E18.5 knock-in (FusÎNLS/ÎNLS), and knock-out (Fus-/-) mice and their control littermates were extracted with Trizol and libraries were prepared for RNA sequencing and RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Generation sequencing (RASL-seq) (Li et al. 2012; Zhou et al. 2012). For the RNA-seq experiment, biological replicates were used with n=4-5 knock-in animals per group (4 wild-type and 5 homozygous FusÎNLS) and n=5 knock-out animals per group (5 wild-type and 5 homozygous Fus-/-). For the RASL-seq analysis, biological replicates were used with n=4 knock-in animals per group (4 wild-type, 4 heterozygous and 4 homozygous FusÎNLS) and n=5 animals per group (5 wild-type and 5 homozygous Fus-/- knock-out).
2016-03-14 | E-GEOD-78730 | biostudies-arrayexpress
Project description:To gain insights into the mechanisms of dihydroberberine, sunitinib and dihydroberberine plus sunitinib on inhibition to A549 cells, we have employed whole genome microarray expression profiling as a discovery platform to identify different genes between dihydroberberine, sunitinib and dihydroberberine plus sunitinib-treated sample and control. A549 cells were cultivated in the absence or presence of 25?mol/L dihydroberberine, 2?mol/L sunitinib, 25?mol/L dihydroberberine plus 2?mol/L sunitinib for 48 h, followed by the Agilent Whole Human Genome Oligo Microarray
2015-06-26 | E-GEOD-70282 | biostudies-arrayexpress