Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA197329 | ENA |
REPOSITORIES: ENA
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Project description:We previously showed that the proteasome inhibitor bortezomib (Velcade) induces cell death in a subset of human bladder cancer cell lines. Heat shock protein 72 kDa (Hsp72) is the major cytosolic stress-inducible molecular chaperone, and is thought to protect cells from proteasome inhibition. Here, using whole genome mRNA expression profiling, we identify isoform-specific expression of Hsp72 within a heterogeneous panel of bladder cancer cell lines. Bortezomib induced strong upregulation of both the HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A-high) cells, whereas only HSPA1B isoform expression was induced in UM-UC10 and UM-UC13 (HSPA1A-low) cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1) to the HSPA1A promoter much more efficiently in 253JB-V cells than in UM-UC13, but other HSF1 transcriptional targets were induced in all of the cell lines, implicating a specific defect in HSPA1A induction. Methylation-specific PCR revealed that the HSPA1A promoter was selectively methylated in the HSPA1A-low cell lines (UM-UC10 and UM-UC13), and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B sensitized these cells to bortezomib. Exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib both in vitro and in vivo. Together, our results suggest that a subset of human bladder cancer cells possess epigenetic modifications that shut off the HSPA1A promoter and increases dependency on the HSPA1B isoform to maintain Hsp72 expression. Our data also support the targeting of HSF1 or Hsp72 for use as tools to enhance bortezomib sensitivity in solid tumors.
2013-08-01 | GSE46132 | GEO
Project description:We previously showed that the proteasome inhibitor bortezomib (Velcade) induces cell death in a subset of human bladder cancer cell lines. Heat shock protein 72 kDa (Hsp72) is the major cytosolic stress-inducible molecular chaperone, and is thought to protect cells from proteasome inhibition. Here, using whole genome mRNA expression profiling, we identify isoform-specific expression of Hsp72 within a heterogeneous panel of bladder cancer cell lines. Bortezomib induced strong upregulation of both the HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A-high) cells, whereas only HSPA1B isoform expression was induced in UM-UC10 and UM-UC13 (HSPA1A-low) cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1) to the HSPA1A promoter much more efficiently in 253JB-V cells than in UM-UC13, but other HSF1 transcriptional targets were induced in all of the cell lines, implicating a specific defect in HSPA1A induction. Methylation-specific PCR revealed that the HSPA1A promoter was selectively methylated in the HSPA1A-low cell lines (UM-UC10 and UM-UC13), and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B sensitized these cells to bortezomib. Exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib both in vitro and in vivo. Together, our results suggest that a subset of human bladder cancer cells possess epigenetic modifications that shut off the HSPA1A promoter and increases dependency on the HSPA1B isoform to maintain Hsp72 expression. Our data also support the targeting of HSF1 or Hsp72 for use as tools to enhance bortezomib sensitivity in solid tumors. RNA was isolated from cells using the TRIzol Reagent (Invitrogen/ Life Technologies, Grand Island, NY), followed by cleanup with RNeasy Mini kits (Qiagen, Germantown, MD). RNA was used for the synthesis of biotin-labeled cRNA, which was prepared using the Illumina RNA amplification kit (Ambion/ Life Technologies), and then hybridized to Illumina Human-HT12 (Illumina, Inc., Hayward, CA) chips. Washed chips were scanned with BeadStation 500x (Illumina) and the signal intensities quantified with BeadStudio (Illumina).
2013-08-01 | E-GEOD-46132 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling of parental (native) and 3-bromopyruvate-resistant UM-UC-3 bladder cancer cells. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 450,000 CpGs in treatment-naive and 3-bromopyruvate-resistant UM-UC-3 bladder cancer cells.
2021-05-04 | GSE173764 | GEO
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Project description:To explore the molecular mechanism underlying NONO-mediated lymphatic metastasis inhibition in bladder cancer, a genome-wide RNA-sequencing was conducted to compare gene expression profiles of UM-UC-3 cells with NONO knockdown and control.
2020-03-21 | GSE147323 | GEO
Project description:Genome wide expression analysis of FABP4 modulation in urothelial cancer cell UM-UC14 and UM-UC9
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Project description:Proteomic characterization of bladder cancer cells exposed to medium from tumor-associated macrophages cocultured with bladder cancer cells.
2025-02-20 | PXD049719 | JPOST Repository
Project description:Bladder cancer stem cells (CSCs) contribute to tumorigenesis, recurrence and chemoresistance of bladder cancer. However, the molecular mechanisms underlying their self-renewal are poorly unknown. Long noncoding RNAs (lncRNAs) act as crucial regulators in a lot of human cancers, yet their potential roles and molecular mechanisms in bladder CSCs are poorly understood. The goal of this study is to identify the differentially expressed lncRNAs in bladder CSCs (UM-UC-3 4th spheres), its two differentiation sublines and bladder non-CSCs (UM-UC-3). Our study reveals that deregulation of lncRNAs is involved in the bladder CSCs.
2019-09-22 | GSE107857 | GEO
Project description:To further identify the underlying mechanisms of SLC2A11-MIF in bladder cancer progress, we performed genome-wide RNA expression profile screening in which we compared gene expression profiles in SLC2A11-MIF-knockdown and control cells in T24 or UM-UC-3
2024-08-01 | GSE271133 | GEO