Differential expression of ten-eleven translocation genes in endometrial cancers

Ciesielski, Piotr; Jóźwiak, Paweł; Wójcik‐Krowiranda, Katarzyna; Forma, Ewa; Cwonda, Łukasz; Szczepaniec, Sylwia; Bieńkiewicz, Andrzej; Bryś, Magdalena; Krześlak, Anna

doi:10.1177/1010428317695017

Cited by 32 publications

(45 citation statements)

References 41 publications

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“…These 5mC oxidation products were implicated as intermediates in the conversion of 5mC to unmodified cytosines. Levels of 5hmC have recently been positively correlated with the expression levels of the Tet enzyme family [50]. As shown in Figure 2(g) and in line with our observation that M1 activation is marked with a global increase in 5hmC levels, we found that expression levels of Tet 2 increased significantly during M1 activation.…”

Section: Global Changes In 5mc and 5hmc Levels During M1 Activation Asupporting

confidence: 89%

Global modulation in DNA epigenetics during pro-inflammatory macrophage activation

et al. 2019

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DNA methylation patterns create distinct gene-expression profiles. These patterns are maintained after cell division, thus enabling the differentiation and maintenance of multiple cell types from the same genome sequence. The advantage of this mechanism for transcriptional control is that chemical-encoding allows to rapidly establish new epigenetic patterns 'on-demand' through enzymatic methylation and demethylation of DNA. Here we show that this feature is associated with the fast response of macrophages during their pro-inflammatory activation. By using a combination of mass spectroscopy and single-molecule imaging to quantify global epigenetic changes in the genomes of primary macrophages, we followed three distinct DNA marks (methylated, hydroxymethylated and unmethylated), involved in establishing new DNA methylation patterns during pro-inflammatory activation. The observed epigenetic modulation together with gene-expression data generated for the involved enzymatic machinery may suggest that demethylation upon LPS-activation starts with oxidation of methylated CpGs, followed by excisionrepair of these oxidized bases and their replacement with unmodified cytosine.

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Section: Global Changes In 5mc and 5hmc Levels During M1 Activation Asupporting

confidence: 89%

Global modulation in DNA epigenetics during pro-inflammatory macrophage activation

et al. 2019

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“…A study of hepatocellular carcinoma observed decreased expression of TET1 , but not TET2 and TET3 [ 29 ]. Moreover, decreased TET1 expression correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer [ 30 ]. Similarly, loss of 5hmC in gastric cancer was mainly correlated with the downregulation of TET1 [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Association of TET3 epigenetic inactivation with head and neck cancer

et al. 2018

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The aim of this study was to clarify the epigenetic regulation of ten eleven translocation protein (TET) family genes, which can provide insights into the mechanisms of tumorigenesis and the risk of disease recurrence in head and neck squamous cell carcinoma (HNSCC). We generated methylation profiles of TET1, TET2 and TET3 genes in tumor samples obtained from 233 patients with HNSCC; these included 57 hypopharynx, 44 larynx, 69 oral cavity, and 63 oropharynx tumor samples. The mRNA expression and promoter DNA methylation of TET family genes were examined via quantitative RT-PCR and methylation-specific PCR, respectively. Promoter methylation was compared with various clinical characteristics and the TET methylation index (TE-MI). The TE-MI, representing the number of methylation events in TET family genes, was positively correlated with alcohol consumption (P = 0.004), high-risk human papilloma virus (HPV) status (P = 0.004) and disease recurrence (P = 0.002). The simultaneous methylation analysis of TET family genes was correlated with reduced disease-free survival in unfavorable event groups (log-rank test, P = 0.026). In the multivariate Cox proportional hazards analysis, TET3 methylation in T1 and T2 tumor stages, oropharyngeal cancer, and oral cancer patients exhibited high association with poor survival (hazard ratio: 2.64, P = 0.014; 3.55, P = 0.048; 2.63, P = 0.028, respectively). A joint analysis of the tumor suppressor gene methylation index showed a significant trend toward a higher TE-MI. The methylation status of TET3 was independently associated with aggressive tumor behavior and a global effect on DNA methylation status in HNSCC.

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“…DNA methylation and demethylation are dynamic processes mediated by the DNMT and TET family proteins, respectively. The most important function of TET1 (ten‐eleven translocation) protease activity is to convert 5‐methylcytosine (5‐mC) into 5‐hydroxymethylcytosine (5‐hmC), while the TET2 and TET3 mRNAs do not differ in GC . Tet1 expression was also significantly reduced in CagA + GC tissues compared with that in noncancerous tissues .…”

Section: Discussionmentioning

confidence: 99%

“…The most important function of TET1 (ten-eleven translocation) protease activity is to convert 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC), while the TET2 and TET3 mRNAs do not differ in GC. 29,30,[45][46][47][48][49] Tet1 expression was also significantly reduced in CagA + GC tissues compared with that in noncancerous tissues. 18 According to many studies and experimental data, H pylori infection/CagA promotes the transport of the DNMT1 and DNMT3B proteins (DNA methyltransferase 3 B) into the nucleus of cells, and this may be related to the silencing of transcriptional expression, such as E-cadherin (CDH1) and forkhead box (Fox).…”

Section: T a B L E 2 Helicobacter Pylorimentioning

confidence: 91%

Helicobacter pylori infection leads to KLF4 inactivation in gastric cancer through a TET1‐mediated DNA methylation mechanism

Zhao

Liu

et al. 2020

Cancer Medicine

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Krüppel‐like factor 4 (KLF4) has a tumor suppressor role in the progression of gastric cancer (GC), and inhibition or loss of KLF4 expression was identified in GC. The aim of this study was to explore the new molecular mechanism of KLF4 inactivation in gastric cancer. Herein, we report that Helicobacter pylori infection or Cag pathogenicity island protein A (CagA) gene transduction resulted in KLF4 expression downregulation and promoted gastric epithelial cell and gastric cancel cell proliferation, migration, and colony formation. Mechanistically, we found that CagA gene transduction led to DNA methylation of the KLF4 promoter, an effect that was relevant to the significant downregulation of TET1 expression. Causally, knockdown of TET1 expression decreased KLF4 expression, whereas overexpression of TET1 had the opposite effect. Clinically, we found that KLF4 expression and the 5‐hmC levels were lower in GC cells with H pylori infection than in GC cells without H pylori infection. Thus, our study not only sheds new light on how H pylori infection promotes the progression of GC but also elucidates a novel mechanism of KLF4 inactivation in GC pathogenesis. During pathogenesis, an alteration in the H pylori/CagA‐TET1‐KLF4 signaling pathway plays a critical role, suggesting that this pathway may be a prospective target for gastric carcinoma intervention and therapy.

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Differential expression of ten-eleven translocation genes in endometrial cancers

Cited by 32 publications

References 41 publications

Global modulation in DNA epigenetics during pro-inflammatory macrophage activation

Global modulation in DNA epigenetics during pro-inflammatory macrophage activation

Association of TET3 epigenetic inactivation with head and neck cancer

Helicobacter pylori infection leads to KLF4 inactivation in gastric cancer through a TET1‐mediated DNA methylation mechanism

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