Metabolic recoding of epigenetics in cancer

Wang, Yi-Ping; Lei, Qun-Ying

doi:10.1186/s40880-018-0302-3

Cited by 83 publications

(59 citation statements)

References 96 publications

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“…A prerequisite for the efficacy of PRRT in NETs is an abundance of somatostatin receptor type 2 (SSTR2) expression (3). Epigenetic regulation of gene expression (9) can be modified by histone deacetylase (HDAC) inhibitors and DNA methyl transferase (DNMT) inhibitors (10). The role of epigenetics has been investigated in NETs (11), and preclinical studies have revealed that DNMT inhibitors such as decitabine and HDAC inhibitors such as valproic acid or tacedinaline can upregulate the expression of SSTR2 and enhance somatostatin ligand binding to tumor cells (12,13).…”

mentioning

confidence: 99%

Combination of 5-Fluorouracil with Epigenetic Modifiers Induces Radiosensitization, Somatostatin Receptor 2 Expression, and Radioligand Binding in Neuroendocrine Tumor Cells In Vitro

et al. 2019

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Peptide receptor radionuclide therapy in advanced neuroendocrine tumors (NETs) demonstrates a limited objective response rate. The therapeutic efficacy might be further increased by peptide receptor chemoradionuclide therapy. In this preclinical study, we explored the effects of 5-fluorouracil plus the DNA methyltransferase inhibitor decitabine or the histone deacetylase inhibitor tacedinaline on NET cells in vitro. Methods: Human NET cell lines BON1 and QGP1 were treated with 5-fluorouracil alone or in combination with decitabine or tacedinaline, respectively. Radiosensitivity was tested in combination with γ-irradiation at doses of 0, 2, 4, or 6 Gy by colony formation assay. Somatostatin receptor type 2 (SSTR2) expression and 68 Ga-DOTATOC uptake by human NET cell lines were investigated by Western blot analysis and by a radioligand binding assay. Results: Treatment with 5-fluorouracil alone or in combination with decitabine or tacedinaline reduced tumor cell viability and induced apoptosis, enhanced radiosensitivity in BON1 and QGP1 cells, induced SSTR2 expression, and resulted in increased radioligand binding of 68 Ga-DOTATOC in NET cells. Conclusion: This preclinical study demonstrated that 5-fluorouracil alone or in combination with decitabine or tacedinaline caused radiosensitization of tumor cells, upregulation of SSTR2 expression in tumor cells, and increased radioligand binding of 68 Ga-DOTATOC to these tumor cells. These preclinical in vitro findings indicate that 5-fluorouracil in combination with epigenetic modifiers might be a putative strategy to improve the treatment efficacy of peptide receptor chemoradionuclide therapy in NET. Combination of 5-Fluorouracil with Epigenetic ModifiersInduces Radiosensitization, http://jnm.snmjournals.org/content/60/9/1240 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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confidence: 99%

Combination of 5-Fluorouracil with Epigenetic Modifiers Induces Radiosensitization, Somatostatin Receptor 2 Expression, and Radioligand Binding in Neuroendocrine Tumor Cells In Vitro

et al. 2019

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“…DNA methylation is a critical type of DNA modi cation occurring at the epigenetic level and is modulated by DNA methyltransferases [28]. During cancer development, abnormal methylation often occurs, resulting in abnormal expression of multiple key genes [29]. In this study, hypomethylation of PBK resulted in higher expression of PBK and could be related to poor prognosis in patients with ovarian cancer, suggesting that PBK may act as a biomarker and therapeutic target in ovarian cancer.…”

Section: Discussionmentioning

confidence: 60%

Identification of Molecular Markers Associated With Ovarian Cancer Prognosis Using Bioinformatics Analysis

Chuang¹,

Lyu²,

Liu³

2020

Preprint

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Background Ovarian cancer is associated with a high mortality rate worldwide. However, the pathogenesis, clinicopathological features, and genetic mechanisms of ovarian cancer are still unclear, and it is essential to identify prognostic markers for its clinical diagnosis and treatment. Here, we utilized bioinformatic analysis to identify potential genes involved in mediating BRCA1 expression to elucidate the potential mechanisms underlying ovarian cancer. Methods Gene expression profiling (GSE14407) was performed to identify differentially expressed genes (DEGs) and analyze the weighted gene co-expression network. We selected the key module that was significantly associated with BRCA1 expression and performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for genes in the hub module. We then screened the hub genes utilizing the Search Tool for the Retrieval of Interacting Genes Database (STRING) and Molecular Complex Detection (MCODE) plug-in in Cytoscape. We validated gene expression levels through The Cancer Genome Atlas and GTEx databases for hub genes and screened genes that were related to overall survival in patients with ovarian cancer using the Kaplan-Meier plotter database. Results In total, 3124 DEGs were detected, including 433 upregulated genes and 2691 downregulated genes. We selected the brown module, which was the most significantly associated with BRCA1 expression. GO analysis showed that the hub module genes were significantly enriched in biological processes, including the mitotic cell cycle process, chromosome segregation, and cell division. KEGG analysis showed that the hub module genes were particularly enriched in the cell cycle, p53 signaling pathway, and small cell lung cancer. We selected 30 hub genes from the protein-protein interaction network, which had 88 nodes and 721 edges. Further analyses identified PBK as a prognosis-associated hub gene. Notably, PBK expression was significantly increased in ovarian cancer tissues, as demonstrated by immunohistochemistry analysis using samples from the Human Protein Atlas database.Conclusion PBK was found to be associated with overall survival in patients with ovarian cancer. Our results provide insights into our understanding of the molecular mechanisms and molecular diagnosis of ovarian cancer.

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“…The methylation of promoter regions of particular genes leads to their transcriptional repression [80]. In cancer CpG-rich regions of gene promoters can undergo aberrant hypermethylation, leading to the silencing of gene expression [81]. Evaluating various DNA methylation data sets generated from prostate cancer tissues, we noted [72] that hypermethylated patterns were consistently identified for five PDE4D transcripts, namely PDE4D1, PDE4D2, PDE4D4, PDE4D5 and PDE4D8 and that, in some cases, these regions included the transcriptional start sites (TSS) of such PDE4D isoforms.…”

Section: Early Insights Into Prostate Cancer-regulated Transcription mentioning

confidence: 99%

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

et al. 2019

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Increased PSA-based screening for prostate cancer has resulted in a growing number of diagnosed cases. However, around half of these are ‘indolent’, neither metastasizing nor leading to disease specific death. Treating non-progressing tumours with invasive therapies is currently regarded as unnecessary over-treatment with patients being considered for conservative regimens, such as active surveillance (AS). However, this raises both compliance and protocol issues. Great clinical benefit could accrue from a biomarker able to predict long-term patient outcome accurately at the time of biopsy and initial diagnosis. Here we delineate the translation of a laboratory discovery through to the precision development of a clinically validated, novel prognostic biomarker assay (InformMDx™). This centres on determining transcript levels for phosphodiesterase-4D7 (PDE4D7), an enzyme that breaks down cyclic AMP, a signalling molecule intimately connected with proliferation and androgen receptor function. Quantifiable detection of PDE4D7 mRNA transcripts informs on the longitudinal outcome of post-surgical disease progression. The risk of post-surgical progression increases steeply for patients with very low ‘PDE4D7 scores’, while risk decreases markedly for those patients with very high ‘PDE4D7 scores’. Combining clinical risk variables, such as the Gleason or CAPRA (Cancer of the Prostate Risk Assessment) score, with the ‘PDE4D7 score’ further enhances the prognostic power of this personalized, precision assessment. Thus the ‘PDE4D7 score’ has the potential to define, more effectively, appropriate medical intervention/AS strategies for individual prostate cancer patients.

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Metabolic recoding of epigenetics in cancer

Cited by 83 publications

References 96 publications

Combination of 5-Fluorouracil with Epigenetic Modifiers Induces Radiosensitization, Somatostatin Receptor 2 Expression, and Radioligand Binding in Neuroendocrine Tumor Cells In Vitro

Combination of 5-Fluorouracil with Epigenetic Modifiers Induces Radiosensitization, Somatostatin Receptor 2 Expression, and Radioligand Binding in Neuroendocrine Tumor Cells In Vitro

Identification of Molecular Markers Associated With Ovarian Cancer Prognosis Using Bioinformatics Analysis

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

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