UHRF1 mediates cell migration and invasion of gastric cancer

Zhang, Haixia; Song, Yanli; Chen, Yang; Wu, Xue-Ru

doi:10.1042/bsr20181065

Cited by 19 publications

(14 citation statements)

References 25 publications

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“…UHRF1 antagonism is emerging as a therapeutic strategy in cancer (18, 19, 29–32). Recent genetic studies suggest that inhibition of the UHRF1 SRA–DNA interaction is a strategy for inhibiting tumor suppressor gene silencing in colon cancer cells (18).…”

Section: Discussionmentioning

confidence: 99%

The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation

Vaughan

Rothbart

Dickson

2019

Journal of Biological Chemistry

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The Su(var)3–9, enhancer of zeste, and trithorax (SET) and really interesting new gene (RING) finger–associated (SRA) protein domain is conserved across bacteria and eukaryota and coordinates extrahelical or “flipped” DNA bases. A functional SRA domain is required for ubiquitin-like with PHD and RING finger domains 1 (UHRF1) E3 ubiquitin ligase activity toward histone H3, a mechanism for recruiting the DNA methylation maintenance enzyme DNA methyltransferase 1 (DNMT1). The SRA domain supports UHRF1 oncogenic activity in colon cancer cells, highlighting that UHRF1 SRA antagonism could be a cancer therapeutic strategy. Here we used molecular dynamics simulations, DNA binding assays, in vitro ubiquitination reactions, and DNA methylation analysis to identify the SRA finger loop as a regulator of UHRF1 ubiquitin targeting and DNA methylation maintenance. A chimeric UHRF1 (finger swap) with diminished E3 ligase activity toward nucleosomal histones, despite tighter binding to unmodified or asymmetric or symmetrically methylated DNA, uncouples DNA affinity from regulation of E3 ligase activity. Our model suggests that SRA domains sample DNA bases through flipping in the presence or absence of a cytosine modification and that specific interactions of the SRA finger loop with DNA are required for downstream host protein function. Our findings provide insight into allosteric regulation of UHRF1 E3 ligase activity, suggesting that UHRF1's SRA finger loop regulates its conformation and function.

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Section: Discussionmentioning

confidence: 99%

The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation

Vaughan

Rothbart

Dickson

2019

Journal of Biological Chemistry

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“…The protein UHRF1 encodes a hub protein that integrates epigenetic information. In the study of gastric cancer, the researchers found that the high expression of this gene would enhance the invasion and proliferation of tumor 40 …”

Section: Discussionmentioning

confidence: 99%

Establishment of a prognostic model of four genes in gastric cancer based on multiple data sets

Zhou

et al. 2021

Cancer Medicine

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Gastric cancer (GC) is a kind of malignancy with a high mortality and recurrence. An effective prediction model based on ideal biomarkers to assess prognosis could benefit patients for optimization of treatment. Bioinformatics has played an increasingly important role in the study of cancer diseases. Therefore, this study started with bioinformatics to establish a reliable prognostic model of gastric cancer. The gene expression data and clinical data of GC tissues and normal tissues were obtained from the Gene Expression Omnibus (GEO), Genotype‐Tissue Expression (GTEx), and The Cancer Genome Atlas (TCGA) profile database. We finally identified a four gene signature and constructed a prognostic model. The results of internal and external validation showed that the model is highly reliable. In addition, we also constructed a nomogram based on the model, which was verified by a calibration curve to show its predicted accuracy. Comprehensive analysis indicated that the four genes in the model are related to the occurrence and development of tumors, perhaps they are potential targets for tumor treatment. Generally, this prognostic model can bring potential benefits to patients with gastric cancer.

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“…qRT-PCR was done with Brilliant III Ultra-Fast SYBR Green (Agilent) with ACTB gene as homeobox gene. We used BCL-2 10 , BIRC5 (survivin) 11,12 , Bax 9 , p53 13 , ABCB1 14 , UHRF1 15 , and DNMT1 16 genes for apoptotic effects after thymoquinone and beta-sitosterol treatment.…”

Section: Gene Expressions Assaymentioning

confidence: 99%

“…Previous studies revealed that some DEGs are responsible for carcinoid lesions in the stomach, which are induced by elevations of gene expression such as BCL-2 10 , BIRC5 (survivin) 11,12 , Bax 9 , p53 13 , ABCB1 14 , UHRF1 15 , and DNMT1 16 . These genes are involved by the Hippo BIRC5 pathway, p53 signaling pathway, intrinsic apoptotic pathway that interacts with XIAP and DIABLO leading to caspase-3 and caspase-9 inactivation, or regulators of apoptosis, WNT pathway, UHRF1-dependent regulation, and DNA methyltransferase pathway.…”

Section: Introductionmentioning

confidence: 99%

Antitumor Effects Of Phytochemicals Of Hot Three Plants On Gastric Adenocarcinoma

Ragchaasuren

Tumurkhuu

Byambaa

et al. 2021

Preprint

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BACKGROUNDThymoquinone (TQ) and beta-sitosterol (BS), the bioactive constituents derived from the medicinal plant Atragene sibirica L, Ranunculus repens L, Pulsatilla Bungeana have been used for anti-cancer treatment in Traditional Mongolian Medicine. Recent studies reported that TQ, BS exhibited anti-proliferative effects on several cancer cell lines. This study was performed to investigate the antitumor effects of phytochemicals on gastric adenocarcinoma in vitro.METHODSTo this aim, we performed a cell apoptosis assay WST1 and several cancer-related gene expressions (Bcl, BIRC5, p53, BAX). NCI-N87, MKN74 cells were seeded at a density of 5×104 cells per well in 96-well culture plates. After overnight incubation, the fresh medium containing different concentrations of TQ (20, 40, 60, 80, and 100 mM/ml) and beta-sitosterol (10, 1, 0.1, 0.001, 0.001 mM/ml) were applied. Following a 24-h incubation, the cell viability was determined by WST-1 assay. We also quantified the expression levels of mRNAs of these genes through qRT-PCR experiments.RESULTSOur results showed that TQ induced a higher percentage of cell apoptosis in the human gastric adenocarcinoma cell lines compared to that of control. We observed a significant 4.8-fold change in BAX/BCL2 ratio. These increases were highly correlated with a concentration-dependent manner (p=0.00178). Moreover, the expression of p53 and BIRC5 was downregulated in MKN74 cells after treatment with TQ.CONCLUSIONSOur results demonstrate that TQ effectively inhibits cell proliferation through several gene expressions in vitro. Moreover, inhibition of the downstream molecule of these genes would explain the underlying mechanism of the antitumor activity in cancer cell lines.

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UHRF1 mediates cell migration and invasion of gastric cancer

Cited by 19 publications

References 25 publications

The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation

The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation

Establishment of a prognostic model of four genes in gastric cancer based on multiple data sets

Antitumor Effects Of Phytochemicals Of Hot Three Plants On Gastric Adenocarcinoma

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