Transcriptomic Analysis of Gene Networks Regulated by U11 Small Nuclear RNA in Bladder Cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171744 | GEO | 2021/06/30
REPOSITORIES: GEO
Similar Datasets
Project description:Metastatic urothelial carcinoma of the bladder is generally incurable with current systemic therapies. Chromatin modifiers are frequently mutated in bladder cancer, with ARID1A inactivating mutations present in 20% of tumors. EZH2 is a histone methyltransferase that acts as an oncogene that functionally opposes ARID1A. In addition, PI3K signaling is activated in over 20% of bladder cancers. Here we show that ARID1A-mutant tumors are more sensitive to EZH2 inhibition than ARID1A-wild-type tumors. Mechanistic studies reveal that: 1) ARID1A deficiency results in a dependency on PI3K/AKT/mTOR signaling via upregulation of a non-canonical PI3K regulatory subunit PIK3R3, and: 2) EZH2 inhibitor sensitivity is due to upregulation of PIK3IP1, an inhibitor protein of PI3K signaling. Thus, our studies suggest that a subset of bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K, and reveal novel mechanistic insights into the role of non-canonical PI3K constituents in bladder cancer biology.
2022-08-22 | GSE183777 | GEO
Project description:ARID1A-mutant bladder cancer is dependent on PI3K signaling and is sensitive to EZH2 and/or PI3K inhibition. Clinical trials in molecularly selected patients should be considered.
2022-08-22 | GSE203033 | GEO
Project description:Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine. Potential predictive biomarkers for pictilisib were evaluated and RNA-sequencing was performed to explore drug resistance mechanisms. The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild type PIK3CA. Pictilisib exhibited stronger anti-tumor activity in bladder cancer PDX models with PI3KCA H1047R mutation or amplification than a model with wild-type. Pictilisib synergized with cisplatin and/or gemcitabine in vitro, significantly delayed tumor growth and prolonged survival compared with single drug targeted treatment in the PDX models. The phosphorylation of ribosomal protein S6 correlated with response to pictilisib both in vitro and in vivo, and could potentially serve as biomarker to predict response to pictilisib. The inhibitor activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by co-treatment with the RAF inhibitor sorafenib. RNA-sequencing of tumors resistant to treatment suggested that LSP1 down-regulation might play a role in inducing drug resistance. These preclinical results provide new insight into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer.
2017-10-24 | GSE101419 | GEO
Project description:Transcriptomic Analysis of Gene Networks Regulated by U11 Small Nuclear RNA in Bladder Cancer
| PRJNA720696 | ENA
Project description:<p>One primary bladder cancer and paired peripheral blood sample were subjected to whole genome sequencing on an Illumina HiSeq 2000 platform. This technology was utilized to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations found was a loss-of-function mutation in TSC1 (Tuberous Sclerosis Complex 1), a regulator of mTOR pathway activation. Targeted sequencing using an exon capture and sequencing assay was performed on 13 tumors derived from patients on the same everolimus trial as the index patient and the sequencing data from these tumors is included. TSC1 mutation status was correlated with response to everolimus. The index patient responder tumor and peripheral blood DNA were also subjected to exon capture and sequencing.</p>
| phs000535 | dbGaP
Project description:Background: Neurogenic bladder (NB) after suprasacral spinal cord injury (SSCI) is an interstitial disease with structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs), which have extensive post-transcriptional regulatory functions, widely participate in the pathogenesis of fibrotic diseases and may be promising new biomarkers and potential therapeutic targets. However, the expression profiles and possible roles of circRNAs in bladder fibrosis and NB after SSCI still remain elusive. Methods: Spinal cord transection at the T10–T11 level was used to construct the NB after SSCI model in rats. The bladders were collected in rats without (sham) and with (SSCI 1-3 groups) NB status. Morphological observation was performed to detect the severity of bladder fibrosis. The expression profiles of mRNAs and circRNAs were detected by transcriptome high-through-put sequencing. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different time periods of SSCI were further analyzed. Moreover, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to investigate the potential functions. In addition, the co-expression network (circRNA–miRNA–mRNA) was constructed to understand the internal regulating relationships of these DEMs and DECs. The top ten common expressed DECs in each NB stage were subjected to Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to verify their expression. Results: Bladder weight, smooth muscle cells hypertrophy, and extracellular matrix gradually increased over time after SSCI. Compared with the normal control (NC) group, 3255 DEMs and 1339 DECs, 3449 DEMs and 1324 DECs, 884 DEMs and 1151 DECs were detected in the SSCI 1-3 groups, respectively. Specifically, circRNA3621, circRNA5775, circRNA3111, and circRNA0586 were significant DECs common to SSCI 1–3 compared with NC group. Moreover, GO enrichment suggested that “inflammatory response”, “inflammatory response” and “chronic inflammatory response” were the key events in NB progression. The KEGG pathway related to “Chemokine signaling pathway”, “IL-17 signaling pathway”, and “TGF-beta signaling pathway” were enriched, implying potential roles in regulatory process. Conclusion: This study provides a systematic perspective on the potential functions of these DEMs and DECs during bladder fibrosis process and NB after SSCI, and could help pave the way for effective therapeutics for this devastating and complex disease.
2023-08-18 | GSE227447 | GEO
Project description:We have previously characterized two groups of bladder cancer cell lines based on their dependence on Hedgehog signaling for survival. Here, we examined the global gene expression in these cells. By comparing the gene expression profile within and between these two groups of cells, we identified list of genes and pathways that potentially account for their dependence on Hedgehog signaling, and specifically a gene signature for those cells more dependent to HH signaling for proliferation. We analized four different bladder cancer cell lines: J82, HT1376, T24, and Vmcub1. We performed triplicates of each sample, and completed a Hierarchical Condition Clustering, a Principal Component Analysis, and we also applied statistical analysis to identify genes that are differentially expressed between the different cell lines. We also put these lists of statistically significant genes into a biological context by performing Pathway Analysis.
2012-12-31 | E-GEOD-28255 | biostudies-arrayexpress
Project description:Purpose: To investigate the tumor-promoting role of STIL in bladder cancer. Method: We established the STIL knockout cell line in which the target gene was knocked out by sgRNA. RNA was extracted from cells using trizol reagent(Invitrogen) Result: Through RNA-sequencing analysis of wild-type and STIL-deficient UMUC3 cell lines, the downstream signaling pathways that STIL may be involved in were determined. We found that the PI3K/AKT/mTOR signaling pathway and c-myc were significantly inactivated when STIL was knocked out in bladder cancer. Our RNA-sequencing analysis results showed that the downstream molecules of c-myc (MCM4, HSPD1, EIF2S2, DDX21, DDX18, CBX3, ABCE1) were significantly down-regulated in bladder cancer cells after knockout. Conclusion: STIL enhances the PI3K/AKT/mTOR pathway, which consequently upgraded the expression of c-myc, ultimately promoting the occurrence and progression of bladder cancer C. STIL may suggest potential utility for bladder cancer therapy.
2023-08-01 | GSE211756 | GEO
Project description:Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) has been implicated in the etiology of various human malignant tumors, although its exact role in bladder cancer (BC) remains to be explored. The present study determined the upregulation of MTHFD2 in BC tissues using expression data from The Cancer Genome Atlas (TCGA), a commercial BC tissue microarray (TMA) and patients’ tissues collected by surgery. MTHFD2 expression in patients with BC was frequently associated with worse prognosis, tumor immune cell infiltration and programmed death-ligand 1 (PD-L1) expression. Next, using small interfering RNA, the expression of MTHFD2 in BC cell lines was knocked down, and the results revealed that the tumor cell proliferation and colony-formation abilities were greatly reduced, as well as the expression of PD-L1. In a xenograft nude mouse model, these findings were confirmed. Simultaneously, it was found that abnormal expression of MTHFD2 was closely associated with the PI3K/AKT signaling pathway in both RNA-sequencing and TCGA datasets. This observation was verified in vitro by detecting the protein expression of PI3K and AKT. The activation of PI3K and AKT was enhanced after stimulation with 740Y-P, a PI3K activator, and their cellular activities and PD-L1 expression levels were restored. Finally, it was found that the MTHFD2 levels were positively correlated with chemosensitivity to traditional BC chemotherapeutic agents and various PI3K-AKT-targeted drugs by analyzing the Genomics of Drug Sensitivity in Cancer (GDSC) database. Overall, the present findings revealed that elevation of MTHFD2 was associated with PD-L1 activation in BC via the PI3K/AKT signaling pathway, suggesting that it could be a promising marker of chemotherapy and immunotherapy for BC.
2022-11-17 | GSE217785 | GEO
Project description:Aberrant c-Met activation and upregulation of its cognate ligand HGF are frequently observed in bladder cancer and have been shown to regulate downstream pathways involved in proliferation, motility, and invasion. The precise mechanism underlying HGF/c-MET mediated invasion in bladder cancer is partly addressed by this microarray dataset. HGF activates the canonical TGFb signaling pathway to enhance epithelial mesenchymal transition and bladder carcinoma invasion.
2019-08-23 | GSE104740 | GEO