CircPTK2/PABPC1/SETDB1 axis promotes EMT-mediated tumor metastasis and Gemcitabine resistance in bladder cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA894988 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22064551_1.fastq.gz | Fastqsanger.gz | |||
| SRR22064551_2.fastq.gz | Fastqsanger.gz | |||
| SRR22064552_1.fastq.gz | Fastqsanger.gz | |||
| SRR22064552_2.fastq.gz | Fastqsanger.gz | |||
| SRR22064553_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:To elucidate the specific mechanism by which circPTK2 exerts oncogene functions, we screened the transcriptome by RNA-Seq, focusing on the differential expressed genes in UM-UC-3 and T24 cells with silenced circPTK2 compared to control cells
2023-01-01 | GSE216692 | GEO
Project description:In this research, Human OneArray Microarray analysis was performed to obtain broad spectrum information about the genes differentially expressed in human bladder cancer cell line RT112 and Gemcitabine Resistant Bladder Cancer cell line RT112-Gr.
2015-04-16 | E-MTAB-3495 | biostudies-arrayexpress
Project description:Transcriptional profiling of Oncopig and human bladder cancer cell lines comparing control untreated cells to cell treated with gemcitabine for 48 hours. Goal was to compare similar transcriptional alterations in response to gemcitabine treatment across both species
2024-02-16 | GSE255187 | GEO
Project description:Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance to these chemotherapeutic agents. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In the present study, we showed the expression and role of AR in gemcitabine-resistant bladder cancer cells and examined the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling and network analysis, which revealed increased AR expression and AR-related gene network in T24GR cells. Quantitative RT-PCR and Western blot analysis confirmed increased expression of AR in T24GR cells compared with parental T24 cells, which was associated with more potent transcriptional activity of AR in T24GR cells. The number of AR gene copy in T24GR cells was twice as many as that of T24 cells. Knockdown of AR expression by siRNA resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide also inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. Lastly, the AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Our results suggest that blockade of AR signaling by enzalutamide might be effective for patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.
2016-11-30 | GSE77883 | GEO
Project description:Oncopig and Human Bladder Cancer Cell Lines: Control vs Gemcitabine Treated
| PRJNA1073916 | ENA
Project description:<p>The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human PDAC.</p>
2021-10-15 | MTBLS1925 | MetaboLights
Project description:The progression of conventional urothelial carcinoma (UC) of the bladder to a tumor with a mesenchymal phenotype, referred to as sarcomatoid carcinoma (SARC), is signified by a high propensity for regional and distant metastasis resulting in shorter survival. We report a comprehensive retrospective analysis of 28 cases of SARCs and 84 cases of conventional UCs. A TCGA cohort of 408 muscle-invasive bladder cancers was used as a reference cohort. SARCs showed a distinct mutational landscape with enrichment of p53, PIK3CA, and RB1 mutations. They developed from basal precursor conventional UCs and could be divided into a basal subtype and the most aggressive mesenchymal subtype. Expression analysis showed that SARCs are driven by dysregulation of cell cycle and EMT regulatory networks and nearly half exhibited an immune infiltration phenotype with PDL1 upregulation. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.
2019-05-07 | GSE128192 | GEO
Project description:Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins (PHD) and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element (TE)-derived double-stranded RNAs (dsRNAs), thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.
2024-01-26 | PXD037104 | Pride
Project description:SETDB1, a pivotal histone lysine methyltransferase, has been identified as being transported to the cytoplasm through a CMR1-dependent pathway, contributing to non-histone methylation. However, the function and underlying mechanism of cytoplasmic SETDB1 in breast cancer remain elusive. This study, employing immunohistochemistry, revealed that an elevated level of cytoplasmic SETDB1 is correlated with lymph node metastasis and more aggressive breast cancer subtypes. Functionally, cytoplasmic SETDB1 proves indispensable for cell migration and invasion, as well as the induction of epithelial-mesenchymal transition (EMT), which could be reversed by LMB (a CMR1 inhibitor) treatment. Furthermore, it was observed that cytoplasmic SETDB1 elevates the levels of metabolites associated with the Warburg effect, including glucose, pyruvate, lactate, and ATP. Mechanistically, the release of nuclear SETDB1 alleviates the inhibition of c-MYC transcription, leading to increased c-MYC expression and subsequent up-regulation of LDHA expression. Notably, LDHA overexpression enhanced migration and invasion by inducing EMT, while its depletion can reverse SETDB1-induced migration and invasion, as well as the Warburg effect and EMT. In conclusion, the subcellular localization of cytoplasmic SETDB1 emerges as a pivotal factor in breast cancer progression. This study offers valuable insights into the novel functions and mechanisms of cytoplasmic SETDB1.
2024-03-13 | GSE253717 | GEO
Project description:Spinocerebellar Ataxia Type 2 (SCA2) is caused by expansion of a polyglutamine encoding triplet repeat in the human ATXN2 gene beyond (CAG)31. This is thought to mediate toxic gain-of-function by protein aggregation, and affect RNA processing, resulting in degenerative processes affecting preferentially cerebellar neurons. As a faithful animal model, we generated a knock-in mouse replacing the single CAG of murine Atxn2 with CAG42, a frequent patient genotype. This expansion size was inherited stably. The mice showed phenotypes with reduced weight and later motor incoordination. Although brain Atxn2 mRNA became elevated, soluble ATXN2 protein levels diminished over time, which might explain partial loss-of-function effects. Deficits in soluble ATXN2 protein correlated with the appearance of insoluble ATXN2, a progressive feature in cerebellum possibly reflecting toxic gains-of-function. Since in vitro ATXN2 overexpression was known to reduce levels of its protein interactor PABPC1, we studied expansion effects on PABPC1. In cortex, PABPC1 transcript, soluble and insoluble protein levels were increased. In more vulnerable cerebellum the progressive insolubility of PABPC1 was accompanied by decreased soluble protein levels, with PABPC1 mRNA showing no compensatory increase. The sequestration of PABPC1 into insolubility by ATXN2 function gains was validated in human cell culture. To understand consequences on mRNA processing, transcriptome profiles at medium and old age in three different tissues were studied and demonstrated selective induction of Fbxw8 in old cerebellum. Fbxw8 is encoded next to the Atxn2 locus and was shown in vitro to decrease the level of expanded insoluble ATXN2 protein. In conclusion, our data support the concept that expanded ATXN2 undergoes progressive insolubility and affects PABPC1 by a toxic gain-of-function mechanism with tissue-specific effects, which may be partially alleviated by the induction of FBXW8. Factorial design comparing Atxn2 knock-in mice with wild type littermates in three different tissues (brainstem, cerebellum, liver)
2012-07-24 | E-GEOD-39640 | biostudies-arrayexpress