Decreased expression of ten-eleven translocation 1 protein is associated with some clinicopathological features in gastric cancer

Frycz, Bartosz Adam; Murawa, Dawid; Borejsza-Wysocki, Maciej; Marciniak, Ryszard; Murawa, P.; Drews, Michał; Kołodziejczak, Anna; Tomela, Katarzyna; Jagodzińśki, Paweł P.

doi:10.1016/j.biopha.2013.12.011

Cited by 29 publications

(30 citation statements)

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“…Furthermore, this study also demonstrated that patients with elevated TET2 transcript levels have more favorable overall survival (13). Another previous study demonstrated significantly lower levels of TET1 transcripts and protein in gastric cancer, which was correlated with gender, age and certain clinicopathological features including tumor localization, depth of invasion, lymph node metastasis, histological grade and histological type (17). Du et al (27) used liquid chromatography mass spectrometry/mass spectrometry to demonstrate very low levels of 5-fC and 5-caC and decreased levels of 5-hmC in gastric cancer tissue compared with adjacent non-cancerous tissue.…”

Section: Of Cases ---------------------------------------------------supporting

confidence: 71%

“…The process of methylation has been well characterized in recent years, but the underlying mechanism of demethylation, particularly during carcinogenesis, remains to be elucidated (6,15,16). Ten-eleven translocation (TET) proteins have an important role in DNA demethylation, with reduced expression observed in various tumors (6,13,(17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

“…The TET1 and TET3 proteins use the CXXC zinc motif to bind to5-methylcytosine (5-mC) in CpG islands (16,17,24). The TET proteins have been revealed to catalyze the oxidation of 5-mC to 5-hydroxymethylcytosine Transcript levels of ten-eleven translocation type 1-3 in cervical cancer and non-cancerous cervical tissues (5-hmC) (25).…”

Section: Introductionmentioning

confidence: 99%

“…The TET proteins have been revealed to catalyze the oxidation of 5-mC to 5-hydroxymethylcytosine Transcript levels of ten-eleven translocation type 1-3 in cervical cancer and non-cancerous cervical tissues (5-hmC) (25). Subsequently, 5-hmC is oxidized to 5-formylocytosine (5-fC) and 5-carboxycytosine (5-caC), eventually converting 5-mC to cytosine (13,17,26). This transformation may contribute to unlocking the promoter regions of suppressor genes and facilitating the development of cancer (8,13,16).…”

Section: Introductionmentioning

confidence: 99%

“…This transformation may contribute to unlocking the promoter regions of suppressor genes and facilitating the development of cancer (8,13,16). Low TET expression levels are correlated with decreased 5-hmC levels in malignant tissues and with clinicopathological features in various primary cancer tissues (13,17,20,22,27). However, little is understood regarding the levels of TET expression in cervical cancerous and non-cancerous tissue.…”

Section: Introductionmentioning

confidence: 99%

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Transcript levels of ten-eleven translocation type 1–3 in cervical cancer and non-cancerous cervical tissues

et al. 2017

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Abstract. Decreased expression of ten-eleven translocation (TET1, TET2 and TET3) proteins has been reported in various types of cancer. However, the expression levels of TET proteins in cervical cancer (CC) remain to be elucidated. The present study determined the levels of TET1, TET2 and TET3 transcripts in cancerous (n=80) and non-cancerous cervical tissues (n=41). The results revealed a significant reduction in TET1 transcripts (P=0.0000001) in cervical tissue samples from patients with primary CC compared with samples from control patients. Significantly decreased TET1 transcript levels, as compared to non-cancerous cervical tissues, were also observed in tissue samples with the following characteristics: Stage I (P=0.016), II (P<0.0001), III (P=0.00007) and grade of differentiation G1 (P=0.026), G2 (P=0.00006), G3 (P=0.0007) and Gx (P=0.0004) and squamous histological type (P<0.00001). TET1 transcript levels were significantly lower in patients aged 45-60 years (P=0.0002) and patients age >60 years (P=0.003), as compared with non-cancerous cervical tissues. TET2 transcript levels were lower in cervical cancer tissues classified as stage II (P=0.043) and TET3 transcript levels were lower in stage III samples (P=0.010), tissue samples with a grade of differentiation of G3 (P=0.025) and tissue with squamous type histology (P=0.047), all compared with non-cancerous cervical tissues. The present study demonstrated a significantly reduced level of TET1 transcripts in cancerous cervical tissues, as compared with non-cancerous tissues. Furthermore, decreased TET1-3 transcript levels were identified when patients with CC were stratified by clinicopathological variables, as compared with non-cancerous cervical tissues.

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Section: Of Cases ---------------------------------------------------supporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcript levels of ten-eleven translocation type 1–3 in cervical cancer and non-cancerous cervical tissues

et al. 2017

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TET2 regulates LncRNA‐ANRIL expression and inhibits the growth of human gastric cancer cells

et al. 2016

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Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine in DNA. However, the role of TET enzymes in human gastric cancer remains unknown. Here, we show that TET2 mRNA and protein levels are downregulated in human gastric cancer tissues when compared with normal gastric mucosa. Low expression of TET2 predicts poor overall and disease-free survival. Furthermore, we demonstrate that TET2 inhibits the proliferation and colony formation of human gastric cancer cells by using loss-of-function and gain-of-function strategies. Overexpression of TET2 induces apoptosis in human gastric cancer cells. The mechanism study shows that TET2 binds to the promoter region of the oncogenic long noncoding RNA (lncRNA-ANRIL) and regulates the expression of ANRIL and its downstream genes (INK4a, INK4b, and ARF). Finally, we demonstrate that ANRIL knockdown blocks the effects of TET2 on gastric cancer cell proliferation and colony formation. V C 2016 IUBMB Life, 68(5): [355][356][357][358][359][360][361][362][363][364] 2016

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Clinical significance of DNA methylation mRNA levels of TET family members in colorectal cancer

Rawłuszko-Wieczorek

Siera

Horbacka

et al. 2015

J Cancer Res Clin Oncol

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Purpose Ten eleven translocation (TET) enzyme activity is essential for active DNA demethylation in biological processes, and their altered expression has been observed in various malignancies. Therefore, we investigated DNA methylation and mRNA levels of all TETs in colorectal cancer (CRC) patients.MethodsTET mRNA levels were evaluated using quantitative RT-PCR in primary cancerous and histopathologically unchanged colorectal tissues from patients who underwent radical surgical colon resection (n = 113). DNA methylation levels of the TET CpG island were assessed using bisulfite DNA sequencing and high-resolution melting analysis.ResultsWe found reduced transcript levels of TET1, TET2 and TET3 in cancerous tissue compared with their histopathologically unchanged counterparts (p = 0.000011; p = 0.000001; p = 0.00031, respectively). Importantly, multivariate Cox regression analysis revealed favorable overall survival (OS) and disease-free survival (DFS) outcomes for patients with high TET2 mRNA levels in histopathologically unchanged tissue (HROS = 0.091, 95 % CI 0.011–0.77, p = 0.028; HRDFS = 0.21, 95 % CI 0.04–1.06, p = 0.059). Moreover, we found no DNA methylation in the TET2 and TET3 promoter regions in cancerous and histopathologically unchanged tissue. In contrast, we reported TET1 DNA hypermethylation in a small fraction of patients (n = 12/113).ConclusionTo best of our knowledge, our study is the first to investigate TET mRNA levels in a cohort of CRC patients and correlate them with patients’ prognosis. Present study provides the evidence that TET2 mRNA expression may be an independent prognostic factor for disease recurrence and outcome. Additionally, our findings initially indicate the importance of DNA methylation in regulating TET1 expression.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-014-1901-2) contains supplementary material, which is available to authorized users.

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Decreased expression of ten-eleven translocation 1 protein is associated with some clinicopathological features in gastric cancer

Cited by 29 publications

References 38 publications

Transcript levels of ten-eleven translocation type 1–3 in cervical cancer and non-cancerous cervical tissues

Transcript levels of ten-eleven translocation type 1–3 in cervical cancer and non-cancerous cervical tissues

TET2 regulates LncRNA‐ANRIL expression and inhibits the growth of human gastric cancer cells

Clinical significance of DNA methylation mRNA levels of TET family members in colorectal cancer

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