Role of ZHX2 in VSMCs
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ABSTRACT:
PROVIDER: PRJNA1023573 | ENA |
REPOSITORIES: ENA
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Project description:Primary rat VSMCs were infected with Ad-Control and Ad-ZHX2 and stimulated with PDGF-BB of 24h. RNAseq and differential expression analysis were performed to investigate the role of ZHX2 in VSMCs.
2023-10-07 | GSE244564 | 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:Role of ZHX2 in VSMCs [RNA-seq]
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Project description:Role of ZHX2 in VSMCs [Chip-seq]
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Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-07 | GSE244565 | GEO
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
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:Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. Due to its heterogeneity and lack of hormone receptors or HER2 expression, it is critical to identify novel therapeutic targets in TNBC. Analysis of copy number and gene expression in tumors from The Cancer Genome Atlas suggested that ZHX2 was amplified and overexpressed in breast cancer patients. Correspondingly, we found that ZHX2 was highly expressed in TNBC cell lines and TNBC patient tissues. Functionally, depletion of ZHX2 inhibited TNBC cell growth and invasion in vitro, orthotopic tumor growth and spontaneous lung metastasis in vivo. Mechanistically, ZHX2 bound with Hypoxia inducible factor (HIF) family members and positively regulated HIF1 activity in TNBC by using loss-of-function or gain-of-function studies. Our integrated ChIP-Seq and gene expression profiling demonstrated that ZHX2 co-occupied with HIF1 on transcriptionally active promoters marked by H3K4me3 and H3K27Ac, therefore promoting gene expression. Furthermore, structural simulation and functional studies revealed that multiple residues (R491, R581 and R674) are important in regulating the phenotype of ZHX2 on TNBC tumorigenic potential, which correspond with their roles on controlling HIF1 activity in TNBC cells. These studies establish that ZHX2 activates oncogenic HIF1 signaling, therefore serving as a potential therapeutic target for TNBC.
2021-05-25 | GSE175487 | GEO
Project description:Loss of contractility and acquisition of an epithelial phenotype of vascular smooth muscle cells (VSMCs) are key events in proliferative vascular pathologies such as atherosclerosis and post-angioplastic restenosis. There is no proper cell culture system allowing VSMC differentiation so that it is difficult to delineate the molecular mechanism responsible for proliferative vasculopathy. We investigated whether a micro-patterned substrate could restore the contractile phenotype of VSMCs in vitro. To induce and maintain the differentiated VSMC phenotype in vitro, we introduced a micro-patterned groove substrate to modulate the morphology and function of VSMCs.
2013-11-14 | E-MTAB-1888 | biostudies-arrayexpress