Genistein demethylates the promoter of CHD5 and inhibits neuroblastoma growth in vivo

Li, Hui; Xu, Weijue; Huang, Yimin; Xiong, Hanzhen; Xu, Lingcang; Lv, Zhibao

doi:10.3892/ijmm.2012.1118

Cited by 48 publications

(23 citation statements)

References 37 publications

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“…The promising therapeutic implications of restoring CHD5 expression in neuroblastoma has previously been shown by the reduced clonogenicity and xenograft tumor growth of neuroblastoma cell lines stably transfected with CHD5 cDNA (Fujita et al, 2008). Very recently, genistein has been reported to demethylate the CHD5 promoter, enhance the expression of CHD5 and p53, and inhibit neuroblastoma growth in vivo (Li et al, 2012b). …”

Section: P53mentioning

confidence: 99%

p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance

Chen¹,

Tweddle²

2012

Front. Oncol.

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Neuroblastoma is the most common extra-cranial solid tumor of childhood. Despite significant advances, it currently still remains one of the most difficult childhood cancers to cure, with less than 40% of patients with high-risk disease being long-term survivors. MYCN is a proto-oncogene implicated to be directly involved in neuroblastoma development. Amplification of MYCN is associated with rapid tumor progression and poor prognosis. Novel therapeutic strategies which can improve the survival rates whilst reducing the toxicity in these patients are therefore required. Here we discuss genes regulated by MYCN in neuroblastoma, with particular reference to p53, SKP2, and DKK3 and strategies that may be employed to target them.

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Section: P53mentioning

confidence: 99%

p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance

Chen¹,

Tweddle²

2012

Front. Oncol.

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“…Tumor suppressor genes such as retinoic acid receptor and p16 Ink4 were reactivated by demethylation of CpG sites by genistein in esophageal cancer cells [Fang et al, ]. In neuroblastoma tumor models, genistein decreased hypermethylation of CHD5, and p53 which subsequently inhibited tumor growth [Li et al, ].…”

Section: Discussionmentioning

confidence: 99%

Context Dependent Regulation of Human Phosphoenolpyruvate Carboxykinase Isoforms by DNA Promoter Methylation and RNA Stability

Seenappa

Das

Joshi

et al. 2016

J of Cellular Biochemistry

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Cytoplasmic and mitochondrial isoforms of phosphoenolpyruvate carboxykinase (PEPCK-C and PEPCK-M) regulate hepatic gluconeogenesis to control systemic glucose homeostasis. Transcriptional and post-transcriptional mechanisms may govern synthesis, maintenance and cooperative function of compartmentalized PEPCK enzymes. In a comparative analysis, we show that tumor cells consistently transcribe and translate higher levels of enzymatically active PEPCK-C than PEPCK-M and both the isoforms were present at lower levels in normal fibroblasts. Unlike in PEPCK-M, absence of glucose reduced the PEPCK-C mRNA and protein levels only in HepG2 cells. Interestingly, isoflavone genistein significantly increased PEPCK-C mRNA and protein levels in normal fibroblasts indicating cell type specific control mechanisms. Genistein also significantly affected RNA stability of PEPCK-C but not PEPCK-M in HepG2 cells. This was due to the conserved and functional mRNA destabilizing AU rich sequences at the 3'-UTR region of PEPCK-C gene and was confirmed by luciferase reporter assays suggesting that glucose deprivation and genistein targets these sequences for mRNA degradation in HepG2 cells but not in fibroblasts. Analysis of promoter methylation by luciferase reporter assays and bisulfite DNA sequencing suggested that PEPCK-C but not PEPCK-M promoter was activated by 5-aza-2-deoxycytidine by inducing cytosine demethylation at the specific CpG dinucleotides of 5'-UTR region. Taken together, our data suggests stable PEPCK-M activity and identifies intricate relationship between (1) mRNA stability and (2) promoter DNA methylation as two mechanisms of gene expression that distinguishes PEPCK-C and PEPCK-M enzyme activities in a context and cell type dependent manner during gluconeogenesis. J. Cell. Biochem. 117: 2506-2520, 2016. © 2016 Wiley Periodicals, Inc.

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“…CHD5 responds to environmental cues, for example genestein—a compound present in soybeans—enhances CHD5 expression (Li et al 2012). In neuroblastoma cells in which CHD5 is silenced by promoter methylation, genestein inhibits expression of the DNA methyltransferase DNMT3B, thereby reducing CHD5 methylation and activating its transcription.…”

Section: Subfamily Ii: Chd3 Chd4 Chd5mentioning

confidence: 99%

“…Loss of function CHD5 lesions including compromised expression, promoter hypermethylation, deletion and/or mutation have been reported in glioma (Bagchi et al 2007; Mulero-Navarro and Esteller 2008; Wang et al 2013), neuroblastoma (Fujita et al 2008; Garcia et al 2010; Koyama et al 2012; Li et al 2012), lung cancer (Zhao et al 2012), prostate cancer (Robbins et al 2011), breast cancer (Mulero-Navarro and Esteller 2008; Wu et al 2012), pancreatic adenocarcinoma (Hall et al 2014), gastric cancer (Wang et al 2009; Qu et al 2013), bladder cancer (Wu et al 2015), ovarian cancer (Gorringe et al 2008; Wong et al 2011), gallbladder carcinoma (Du et al 2013), colorectal cancer (Mulero-Navarro and Esteller 2008; Mokarram et al 2009; Cai et al 2012; Fatemi et al 2014), hepatocellular carcinoma (Zhao et al 2014; Fang et al 2015; Xie et al 2015) melanoma (Lang et al 2011), leukemia (Zhao et al 2014), and laryngeal squamous cell carcinoma (Wang et al 2011). …”

Section: Subfamily Ii: Chd3 Chd4 Chd5mentioning

confidence: 99%

The Chromodomain Helicase DNA-Binding Chromatin Remodelers: Family Traits that Protect from and Promote Cancer

Mills

2017

Cold Spring Harb Perspect Med

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A plethora of mutations in chromatin regulators in diverse human cancers is emerging, attesting to the pivotal role of chromatin dynamics in tumorigenesis. A recurrent theme is inactivation of the Chromodomain Helicase DNA-binding (CHD) family of proteins—ATP-dependent chromatin remodelers that govern the cellular machinery’s access to DNA, thereby controlling fundamental processes including transcription, proliferation, and DNA damage repair. This review highlights what is currently known about how genetic and epigenetic perturbation of CHD proteins and the pathways they regulate set the stage for cancer, providing new insight for designing more effective anti-cancer therapies.

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Genistein demethylates the promoter of CHD5 and inhibits neuroblastoma growth in vivo

Cited by 48 publications

References 37 publications

p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance

p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance

Context Dependent Regulation of Human Phosphoenolpyruvate Carboxykinase Isoforms by DNA Promoter Methylation and RNA Stability

The Chromodomain Helicase DNA-Binding Chromatin Remodelers: Family Traits that Protect from and Promote Cancer

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