The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer

Zhang, Yanan; Liu, Jie; Lin, Jing; Zhou, Lei; Song, Yuhua; Wei, Bo; Luo, Xiaoli; Chen, Yingjie; Xiong, Jiaxiu; Xu, Xiaowei; Ding, Lihua; Ye, Qinong

doi:10.18632/oncotarget.7126

Cited by 46 publications

(45 citation statements)

References 49 publications

(56 reference statements)

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“…Vascular endothelial growth factor (VEGF) is one of the most important regulators of tumor angiogenesis in breast cancer 34 . As Zhang Y. et al 35 reported that SET7/9, which is recruited by the transcription factor GATA1, can promote VEGF transcription and breast tumor angiogenesis. This evidence indicates that SET7/9 in breast cancer might function as an oncogene through the methylation of histones to activate target gene expression or the methylation of non-histone proteins directly.…”

Section: Discussionmentioning

confidence: 99%

SET7/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21

Zhou

Zhao

et al. 2020

Cell Death Dis

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Although the deregulation of lysine methyltransferase (su(var)-3-9, enhancer-of-zeste, trithorax) domain-containing protein 7/9 (SET7/9) has been identified in a variety of cancers, the potential role of SET7/9 and the molecular events in which it is involved in breast cancer remain obscure. Using the online Human Protein Atlas and GEO databases, the expression of SET7/9 was analyzed. Furthermore, we investigated the underlying mechanisms using chromatin immunoprecipitation-based deep sequencing (ChIP-seq) and quantitative ChIP assays. To explore the physiological role of SET7/9, functional analyses such as CCK-8, colony formation, and transwell assays were performed and a xenograft tumor model was generated with the human breast cancer cell lines MCF-7 and MDA-MB-231. Mass spectrometry, co-immunoprecipitation, GST pull-down, and ubiquitination assays were used to explore the mechanisms of SET7/9 function in breast cancer. We evaluated the expression of SET7/9 in different breast cancer cohorts and found that higher expression indicated worse survival times in these public databases. We demonstrated positive effects of SET7/9 on cell proliferation, migration, and invasion via the activation of Runt-related transcription factor 2 (RUNX2). We demonstrate that tripartite motif-containing protein 21 (TRIM21) physically associates with SET7/9 and functions as a major negative regulator upstream of SET7/9 through a proteasome-dependent mechanism and increased ubiquitination. Taken together, our data suggest that SET7/9 has a promoting role via the regulation of RUNX2, whereas TRIM21-mediated SET7/9 degradation acts as an anti-braking system in the progression of breast cancer.

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Section: Discussionmentioning

confidence: 99%

SET7/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21

Zhou

Zhao

et al. 2020

Cell Death Dis

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“…PAK5-mediated GATA-1 phosphorylation regulates EMT in breast cancer cells. GATA-1 associates with the histone methyltransferase SET7 to promote VEGF transcription and breast tumor angiogenesis [31][32][33]. GATA-1 promotes cell proliferation, migration, and invasion via activating the PI3K/AKT signaling pathway in colorectal cancer [34].…”

Section: Discussionmentioning

confidence: 99%

Sp1 Mediates the Constitutive Expression and Repression of the PDSS2 Gene in Lung Cancer Cells

Chen

Wang

et al. 2019

Genes

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Prenyl diphosphate synthase subunit 2 (PDSS2) is the first key enzyme in the CoQ10 biosynthesis pathway, and contributes to various metabolic and nephritic diseases. It has been reported that PDSS2 is downregulated in several types of tumors and acts as a potential tumor suppressor gene to inhibit the proliferation and migration of cancer cells. However, the regulatory mechanism of PDSS2 expression remains elusive. In the present study, we first identified and characterized the PDSS2 promoter region. We established four different luciferase reporter constructs which mainly cover the 2 kb region upstream of the PDSS2 gene transcription initiation site. Series luciferase reporter assay demonstrated that all four constructs have prominent promoter activity, and the core promoter of PDSS2 is mainly located within the 202 bp region near its transcription initiation site. Transcription factor binding site analysis revealed that the PDSS2 promoter contains binding sites for canonical transcription factors such as Sp1 and GATA-1. Overexpression of Sp1 significantly inhibited PDSS2 promoter activity, as well as its endogenous expression, at both mRNA and protein levels in lung cancer cells. Site-directed mutagenesis assay further confirmed that the Sp1 binding sites are essential for proximal prompter activity of PDSS2. Consistently, a selective Sp1 inhibitor, mithramycin A, treatment repressed the PDSS2 promoter activity, as well as its endogenous expression. Chromatin immunoprecipitation (ChIP) assay revealed that Sp1 binds to the PDSS2 promoter in vivo. Of note, the expression of Sp1 and PDSS2 are negatively correlated, and higher Sp1 expression with low PDSS2 expression is significantly associated with poor prognosis in lung cancer. Taken together, our results strongly suggest the essential role of Sp1 in maintaining the basic constitutive expression of PDSS2, and the pathogenic implication of Sp1-mediated PDSS2 transcriptional repression in lung cancer cells.

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“…In breast cancer patients, histone methyltransferase SET7 and transcription factor GATA1 expression levels were upregulated and positively correlated with VEGFA expression and microvessel number. Furthermore, SET7 associates with GATA1 to promote VEGFA transcription and breast tumor angiogenesis [125]. However, by using ProtoArray system, Cohn et al identified 172 new SETD3 interacting proteins, and further investigation found that SETD3 binds and methylates the transcription factor FoxM1 to inhibit VEGFA expression under hypoxia [126].…”

Section: Histone Methylation In Tumor Angiogenesismentioning

confidence: 99%

Histone methylation and vascular biology

Wei

Zhu

et al. 2020

Clin Epigenet

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The vasculature not only transports oxygenated blood, metabolites, and waste products but also serves as a conduit for hormonal communication between distant tissues. Therefore, it is important to maintain homeostasis within the vasculature. Recent studies have greatly expanded our understanding of the regulation of vasculature development and vascular-related diseases at the epigenetic level, including by protein posttranslational modifications, DNA methylation, and noncoding RNAs. Integrating epigenetic mechanisms into the pathophysiologic conceptualization of complex and multifactorial vascular-related diseases may provide promising therapeutic approaches. Several reviews have presented detailed discussions of epigenetic mechanisms not including histone methylation in vascular biology. In this review, we primarily discuss histone methylation in vascular development and maturity, and in vascular diseases.

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The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer

Cited by 46 publications

References 49 publications

SET7/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21

SET7/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21

Sp1 Mediates the Constitutive Expression and Repression of the PDSS2 Gene in Lung Cancer Cells

Histone methylation and vascular biology

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