Similar Datasets
Project description:Gene expression profiling of 786-O cells with ZHX2 and p65 knockdown
| PRJNA432739 | ENA
Project description:786-0 is a cell line derived from a clear cell renal carcinoma. Previous studies have shown that the 786-O cell line harbors an inactivating mutation in the von-Hippel Lindau (VHL) gene. Mutations in the VHL gene occur in the majority of sporadic clear cell renal cell. To determine how inactivation of the VHL affects cellular functions, we created a derivative of 786-0, which we call 786-VHL in which a functional allele of VHL has been introduced back into the 786-O cell line. The renal cell carcinoma cell line 786-0, which harbors a mutated allele of VHL, was compared to a cell line derived from 786-0, termed 786-VHL, that contains a functional allele of VHL. Genes whose expression characteristics were dependent on functional VHL were identified.
2010-06-23 | E-GEOD-22256 | biostudies-arrayexpress
Project description:786-0 is a cell line derived from a clear cell renal carcinoma. Previous studies have shown that the 786-O cell line harbors an inactivating mutation in the von-Hippel Lindau (VHL) gene. Mutations in the VHL gene occur in the majority of sporadic clear cell renal cell. To determine how inactivation of the VHL affects cellular functions, we created a derivative of 786-0, which we call 786-VHL in which a functional allele of VHL has been introduced back into the 786-O cell line.
2010-06-10 | GSE22256 | GEO
Project description:Clear cell renal cell carcinoma (ccRCC) is characterized by loss of tumor suppressor Von Hippel Lindau (VHL) function. VHL is the component of E3 ligase complex that promotes the ubiquitination and degradation of hypoxia inducible factor alpha (including HIF1alpha and HIF2alpha) and Zinc Fingers And Homeoboxes 2 (ZHX2). Our recent research showed that ZHX2 contributed to ccRCC tumorigenesis in a HIF independent manner. However, it remains unknown whether ZHX2 can be regulated through deubiquitination. Here we performed a deubiquitinase (DUB) cDNA library binding screen and identified USP13 as a novel DUB that bound ZHX2 and promoted ZHX2 deubiquitination. As a result, USP13 promoted ZHX2 protein stability in an enzymatically dependent manner and depletion of USP13 led to ZHX2 downregulation in ccRCC. Functionally, USP13 depletion led to decreased cell proliferation measured by 2-D colony formation and 3-D anchorage independent growth. USP was a critical effector on maintaining kidney tumorigenesis in an orthotopic xenograft model and its depletion led to both decreased primary kidney tumorigenesis and spontaneous lung metastasis. Our results suggest that USP13 is a potential new therapeutic target in ccRCC.
2022-07-27 | GSE186717 | GEO
Project description:Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bound VHL only when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased ZHX2 amount and nuclear localization. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated ChIP-Seq and microarray analysis showed that ZHX2 promoted NF-kB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
2018-07-19 | GSE109953 | GEO
Project description:The human renal cancer cell line 786-0 was transfected with 3 vectors allowing the doxycycline-inducible expression of 1) the full length wild type sequence of VHL: 786-0 VHL WT, VHL+/+, 2) the R167Q mutant : 786-0 R167Q, VHL mutated, 3) the empty vector : 786-0 EV, VHL-/-. The aim of the study was to examine whether the VHL-R167Q mutation, which is associated with a high risk of developping clear cell renal carcinomas, could impact the plasticity of renal carcinoma cells.
2021-12-09 | E-MTAB-11168 | biostudies-arrayexpress
Project description:We present transcriptome profiling of 786-0 renal cell carcinoma cell lines both with and without Everolimus, an mTOR inhibitorhbn
2022-12-01 | GSE99875 | GEO
Project description:In order to explore the biological function and molecular mechanism of ZHX2 in VSMCs,in this study, we overexpressed ZHX2 in primery VSMCs used chromatin immunoprecipitation sequencing (ChIP-seq) methods to systematically investigate the downstream targets of ZHX2.
2023-10-07 | GSE244563 | GEO
Project description:While early stages of clear cell renal cell carcinoma (ccRCC) are curable, survival outcome for metastatic ccRCC remains poor. The purpose of the current study was to apply a new individualized bioinformatics analysis (IBA) strategy to these transcriptome data in conjunction with Gene Set Enrichment Analysis of the Connectivity Map (C-MAP) database to identify and reposition FDA-approved drugs for anti-cancer therapy. We demonstrated that one of the drugs predicted to revert the RCC gene signature towards normal kidney, pentamidine, is effective against RCC cells in culture and in a RCC xenograft model. Most importantly, pentamidine slows tumor growth in the 786-O human ccRCC xenograft mouse model. To determine which genes are regulated by pentamidine in a human RCC cell line, 786-O, we treated these cells with pentamidine and performed transcriptional profiling analysis. We used microarrays to determine the set of genes regulated by pentamidine in 786-O renal cell cancer cells. Total RNA was isolated from 786-O cells treated with 25 μM pentamidine or vehicle control (DMSO) for 6 hours and hybridized to Affymetrix microarrays.
2014-08-05 | E-GEOD-54709 | biostudies-arrayexpress
Project description:The liver has an exceptional capacity for regeneration which is crucial for maintaining liver function. Since transcriptional regulation of genes controlling metabolism and cell division is a hallmark of liver regeneration (LR), we investigated the role of Zinc-finger and homeboxes 2 (ZHX2), a transcription factor critical for regulating liver postnatal gene expression and hepatic lipid hemostasis, in LR. Our results show that hepatocyte-specific Zhx2 knockout (Zhx2-KOhep) enhances LR after 2/3 partial hepatectomy in mice. Proteomics assays revealed higher mitochondrial oxidative phosphorylation (OXPHOS) in Zhx2-KOhep mouse livers. Oxygen consumption rate (OCR) and ATP generation assays confirmed the enhanced OXPHOS in Zhx2-KOhep mouse livers and human hepatocytes with ZHX2 knockdown.
2023-10-17 | PXD027897 | Pride