Transmembrane protein 88 (TMEM88) promoter hypomethylation is associated with platinum resistance in ovarian cancer

León, María; Cárdenas, Horacio; Vieth, Edyta; Emerson, Robert E.; Segar, Matthew W.; Liu, Yunlong; Nephew, Kenneth P.; Matei, Daniela

doi:10.1016/j.ygyno.2016.06.017

Cited by 56 publications

(51 citation statements)

References 35 publications

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“…Early studies on breast and ovarian cancer cell lines reported sensitivity to platinum-based chemotherapy in cells with either mutant or hypermethylated BRCA1 [88–90]. More recently, several studies have examined DNA methylation and chemoresistance [11,91,92] or survival [93–95] using genome-wide approaches (Table 3). One study, using a custom microarray [92], identified 749 CpG loci that diﬀered in methylation between resistant and sensitive HGSOC, 509 were within promoter regions.…”

Section: Clinical Aspects Of Epigenetics In Eocmentioning

confidence: 99%

“…They used a short hairpin RNA screen (which silences target genes via RNA interference) to examine the eﬀect on carboplatin sensitivity in ovarian cancer cell lines (a normal human surface epithelial line and two EOC lines resistant to carboplatin), and identified 19 genes associated with carboplatin resistance. De Leon et al [91] examined methylation changes in A2780 (ovarian carcinoma) cell line xenografts, treated with carboplatin or control diluent. Six genes had altered methylation of which two hypomethylated genes, TMEM88 and DAXX , had an associated increase in gene expression in platinum resistant xenografts.…”

Section: Clinical Aspects Of Epigenetics In Eocmentioning

confidence: 99%

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Epigenetics in ovarian cancer

Natanzon

Goode

Cunningham

2018

Seminars in Cancer Biology

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Ovarian cancer is a disease with a poor prognosis and little progress has been made to improve treatment. It is now recognized that there are several histotypes of ovarian cancer, each with distinct epidemiologic and genomic characteristics. Cancer therapy is moving beyond classical chemotherapy to include epigenetic approaches. Epigenetics is the dynamic regulation of gene expression by DNA methylation and histone post translational modification in response to environmental cues. Improvement in technology to study DNA methylation has enabled a more agnostic approach and, with larger samples sets, has begun to unravel how epigenetics contributes to the etiology, response to chemotherapy and prognosis in of ovarian cancer. Investigations into histone modifications in ovarian cancer are more nascent. Much more is needed to be done to fully realize the potential that epigenetics holds for ovarian cancer clinical care.

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Section: Clinical Aspects Of Epigenetics In Eocmentioning

confidence: 99%

Section: Clinical Aspects Of Epigenetics In Eocmentioning

confidence: 99%

Epigenetics in ovarian cancer

Natanzon

Goode

Cunningham

2018

Seminars in Cancer Biology

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“…All 4 CpGs within 500 bps upstream of the SNP showed increased methylation (beta value increased from 6.2% to 52%, 8.8% to 55%, 6.2% to 44% and 17% to 56%, respectively). Hypomethylation in the SLC12A4 promoter is related to resistance to platinum-based chemotherapy in ovarian cancer 67 ; the 4 CpGs affected by the SNP are located in the SLC12A4 promoter, suggesting a mechanism of how the SNP may affect response to chemotherapy through regulation of local DNA methylation. More examples of SNP-induced methylation change through disrupting UMs are shown in Figure S3B.…”

Section: Snps Occurring At Identified Dna Motif Sites Is Associated Wmentioning

confidence: 99%

Identification of DNA motifs that regulate DNA methylation

Wang¹,

Zhang²,

Ngo³

et al. 2019

Preprint

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DNA methylation is an important epigenetic mark but how its locus-specificity is decided in relation to DNA sequence is not fully understood. Here, we have analyzed 34 diverse wholegenome bisulfite sequencing datasets in human and identified 313 motifs, including 92 and 221 associated with methylation (methylation motifs, MMs) and unmethylation (unmethylation motifs, UMs), respectively. The functionality of these motifs is supported by multiple lines of evidences. First, the methylation levels at the MM and UM motifs are respectively higher and lower than the genomic background. Second, these motifs are enriched at the binding sites of methylation modifying enzymes including DNMT3A and TET1, indicating their possible roles of recruiting these enzymes. Third, these motifs significantly overlap with SNPs associated with gene expression and those with DNA methylation. Fourth, disruption of these motifs by SNPs is associated with significantly altered methylation level of the CpGs in the neighbor regions. Furthermore, these motifs together with somatic SNPs are predictive of cancer subtypes and patient survival. We revealed some of these motifs were also associated with histone modifications, suggesting possible interplay between the two types of epigenetic modifications. We also found some motifs form feed forward loops to contribute to DNA methylation dynamics. Results Defining DNA methylation regions and de novo motif discoveryWe aimed to identify DNA motifs associated with DNA methylation and thus started with searching for methylation regions that have the strongest signals. We collected whole genome bisulfite sequencing (WGBS) data of 34 human methylomes generated by the NIH Roadmap Epigenomics Project 15,16 (Figure 1A). We took an approach similar to the Ziller et al. study 17 and defined 1.55 million methylation regions containing 11.5 million CpG sites in the 34 methylomes. Because the methylome data is noisy, we only considered regions containing 2 or more CpGs within 400 bp apart, which covers 29.2% of the human genome.

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“…Recently, hypomethylation of some genes has been related to platinum resistance in ovarian cancer (de Leon et al, 2016). Recently, hypomethylation of some genes has been related to platinum resistance in ovarian cancer (de Leon et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Epigenetic deregulation has been considered as a factor conferring tumoral chemo-resistance. Recently, hypomethylation of some genes has been related to platinum resistance in ovarian cancer (de Leon et al, 2016). Teneleven translocation (TET) methylcytosine dioxygenase family catalyzes 5-methylcytosine (5-mC) to 5-hydro-methylcytosine (5-hmC) in an iron and a-ketoglutarate dependent manner, thereby facilitating CpG islands demethylation in mammals (Tahiliani et al, 2009;Zhang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

TET1 promotes cisplatin‐resistance via demethylating the vimentin promoter in ovarian cancer

Han

Zhou

You

et al. 2017

Cell Biology International

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The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells. Ectopic expression of TET1 in A2780 cells promoted cisplatin resistance and decreased cytotoxicity induced by cisplatin, while inhibition of TET1 by siRNA transfection in CP70 cells attenuated cisplatin resistance and enhanced cytotoxicity of cisplatin. Increased TET1 induced re-expression of vimentin through active DNA demethylation, and cause partial epithelial-to-mesenchymal (EMT) in A2780 cells. Contrarily, knocking down of TET1 in CP70 cells reduced vimentin expression and reversed EMT process. Immunohistochemical analysis of TET1 in human ovarian cancer tissues revealed that TET1 existed in nucleus and cytoplasm in ovarian cancer tissues. And the expression of nuclear TET1 was positively correlated with residual tumor and chemotherapeutic response. Thus, TET1 expression causes resistance to cisplatin and one of the targets of TET1 action is vimentin in ovarian cancer.

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Transmembrane protein 88 (TMEM88) promoter hypomethylation is associated with platinum resistance in ovarian cancer

Cited by 56 publications

References 35 publications

Epigenetics in ovarian cancer

Epigenetics in ovarian cancer

Identification of DNA motifs that regulate DNA methylation

TET1 promotes cisplatin‐resistance via demethylating the vimentin promoter in ovarian cancer

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