Diosmin inhibits glioma growth through inhibition of autophagic flux
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ABSTRACT:
PROVIDER: PRJNA729518 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RNA microarray was performed from glioma cell LN229 and GBM8401 that were treated with Diosmin (160 nM) for 48hr in comparison to DMSO vehicle control.
2022-03-24 | GSE174363 | GEO
Project description:Miz1 is required to maintain autophagic flux
| PRJNA210788 | ENA
Project description:Miz1 is a zinc finger protein that regulates expression of cell cycle inhibitors as part of a complex with Myc. Cell cycle-independent functions of Miz1 are poorly understood. Here, we use a Nestin-Cre transgene to delete an essential domain of Miz1 in the central nervous system (Miz1M-NM-^TPOZNes). Miz1M-NM-^TPOZNes mice display cerebellar neurodegeneration characterized by the progressive loss of Purkinje cells. Chromatin immunoprecipitation sequencing and biochemical analyses show that Miz1 activates transcription upon binding to a non-palindromic sequence present in core promoters. Target genes of Miz1 encode regulators of autophagy and proteins involved in vesicular transport that are required for autophagy. Miz1M-NM-^TPOZ neuronal progenitors and fibroblasts show reduced autophagic flux. Consistently, polyubiquitinated proteins and p62/Sqtm1 accumulate in the cerebella of Miz1M-NM-^TPOZNes mice, characteristic features of defective autophagy. Our data suggest that Miz1 may link cell growth and ribosome biogenesis to the transcriptional regulation of vesicular transport and autophagy. ChIP-Seq with H190 and G18 on an Illumina Genome Analyzer IIx.
2013-09-27 | E-GEOD-48602 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5790487 | biostudies-literature
Project description:Miz1 is a zinc finger protein that regulates expression of cell cycle inhibitors as part of a complex with Myc. Cell cycle-independent functions of Miz1 are poorly understood. Here, we use a Nestin-Cre transgene to delete an essential domain of Miz1 in the central nervous system (Miz1ΔPOZNes). Miz1ΔPOZNes mice display cerebellar neurodegeneration characterized by the progressive loss of Purkinje cells. Chromatin immunoprecipitation sequencing and biochemical analyses show that Miz1 activates transcription upon binding to a non-palindromic sequence present in core promoters. Target genes of Miz1 encode regulators of autophagy and proteins involved in vesicular transport that are required for autophagy. Miz1ΔPOZ neuronal progenitors and fibroblasts show reduced autophagic flux. Consistently, polyubiquitinated proteins and p62/Sqtm1 accumulate in the cerebella of Miz1ΔPOZNes mice, characteristic features of defective autophagy. Our data suggest that Miz1 may link cell growth and ribosome biogenesis to the transcriptional regulation of vesicular transport and autophagy.
2013-09-27 | GSE48602 | GEO
Project description:Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g. via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions. Here, we show that both Staticic 3D growth and 3D growth within a bioreactor system modulate key hallmarks of cancer cells, including proliferation and cell death as well as macroautophagy, a recycling pathway often activated by highly proliferative tumors to cope with metabolic stress. The autophagy-related gene expression profiles of 2D- and 3D-grown cells are substantially different, with the 3D-grown cells exhibiting an expression profile closely resembling the (patho-) physiological Statice of a tumor. Underscoring the importance of this pathway, autophagy-controlling transcription factors, such as TFEB and FOXO3, are upregulated in tumors, and 3D-grown cells have increased expression compared with cells grown in 2D conditions. Three-dimensional cultures depleted of the autophagy mediators BECN1, ATG5 or ATG7 or the transcription factor FOXO3, are more sensitive to cytotoxic treatment. Accordingly, combining cytotoxic treatment with compounds affecting late autophagic flux, such as chloroquine, renders the 3D-grown cells more susceptible to therapy and increases intracellular doxorubicin concentration to the level of 2D-grown cells. Altogether, 3D cultures are a valuable tool to study drug response of tumor cells, as these models recapitulate (patho-) physiologically relevant pathways, such as autophagy.
2017-07-04 | GSE100020 | GEO
Project description:MICU1 orchestrates the autophagic flux in a SPGL1- and VPS39-dependent manner
| PRJNA714052 | ENA
Project description:Autophagic flux is associated with chemoresistance, the leading cause of chemotherapeutic failure. Here, we showed that HAX-1 promotes chemoresistance by effectively blocking the fusion of autophagosomes with lysosomes. Mass spectrometric and functional studies demonstrated that HAX-1 recruited NEDD4 to promote Rab7a degradation and inhibited the binding of Rab7a with SNAREs by competitively binding to it. Furthermore, HAX-1 could bind to IGF2BP1 mRNA, thereby contributing to its stability and translation. Moreover, IGF2BP1 enhanced HAX-1 m6A methylation, thereby enhancing its stability. Via in vivo and in vitro experiments, we confirmed the positive role of the IGF2BP1-HAX-1 feedback loop in chemoresistance. Our data provide evidence that HAX-1, IGF2BP1, and SQSTM1 levels are useful predictors of clinical outcome and chemoresistance risk. In addition, our data provide new insights into the clinical applications of therapies related to autophagic flux and its associated molecular network in targeting cisplatin chemoresistance in nasopharyngeal carcinoma.
2023-09-30 | GSE244097 | GEO
Project description:The arginylation branch of the N-end rule pathway positively regulates cellular autophagic flux and clearance of proteotoxic protein
2016-09-27 | PXD003813 | Pride
Project description:Glioblastoma (GBM) carries a dismal prognosis largely due to acquired resistance to the standard treatment, which incorporates the chemotherapy temozolomide (TMZ). Inhibiting the proteasomal pathway is an emerging strategy, where combination treatments are under clinical investigation. We hypothesized that pre-treatment of GBM with bortezomib (BTZ) might sensitize glioblastoma to TMZ by abolishing autophagy survival signals to augment DNA damage and apoptosis. P3 patient-derived GBM cells as well as the tumor cell lines U87, HF66, A172 and T98G were investigated for clonogenic survival after single or combined treatment with TMZ and BTZ in vitro. Change in autophagic flux was examined after experimental treatments in conjunction with inhibitors of autophagy or downregulation of autophagy-related genes -5 and -7 (ATG5 and ATG7, respectively). Autophagic flux was increased in TMZ-resistant P3 and T98G cells as indicated by diminished levels of the autophagy markers LC3A/B-II and increased STX17, higher protein degradation and no formation of p62 bodies nor induction of apoptosis. In contrast, BTZ treatment attenuated ULK1 mRNA, total and phosphorylated protein, and accumulated LC3A/B-II, p62 and autophagosomes analogously to Baf1 and chloroquine autophagy inhibitors. These autophagosomes did not fuse with lysosomes, indicated by attenuated STX17 expression and reduced degradation of long-lived proteins, which culminated in enhanced caspase-3/8 dependent apoptosis. BTZ synergistically enhanced TMZ efficacy, attenuated tumor cell proliferation, triggered ATM/Chk2 DNA damage signalling to further augment caspase-3/8 mediated apoptosis in the TMZ resistant P3 and T98G GBM cells. Genetic or chemical inhibition of autophagy (with CRISPR-CAs9 ATG5, ATG7 shRNA, MRT68921 or VPS34-IN1) abrogated BTZ efficacy and rescued BTZ+ TMZ treated GBM cells from death. We conclude that Bortezomib ameliorates temozolomide resistance through ATG5/7-dependent abrogated autophagic flux and may be amenable in combination treatment regimens for TMZ refractory GBM patients.
2023-03-10 | PXD021828 | Pride