Impact on clinical prognosis using DNA methylation of the SLC16A3 promoter and expression of the human lactate transporter MCT4 in renal cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 452-452
Author(s):  
Jens Bedke ◽  
Pascale Fisel ◽  
Stefan Winter ◽  
Stephan Kruck ◽  
Marcus Scharpf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Protein Expression ◽  
Mrna Expression ◽  
Promoter Activity ◽  
Epigenetic Mechanism ◽  
Monocarboxylate Transporter ◽  
Clinical Prognosis ◽  
Cpg Sites ◽  
Promoter Dna Methylation ◽  
Promoter Dna

452 Background: The monocarboxylate transporter 4 (MCT4) is a metabolic target in tumor biology because it mediates lactate transport across membranes resulting in antiapoptotic effects. Cell experiments support the importance of MCT4 in clear cell renal cell carcinoma (ccRCC). In this study, we assessed the prognostic potential of MCT4 expression in ccRCC and its epigenetic regulation by DNA methylation as novel predictive marker for patient outcome using independent ccRCC cohorts. Methods: MCT4 protein expression was quantified in 207 ccRCC and corresponding nontumor tissues. Data of an independent ccRCC cohort from The Cancer Genome Atlas (TCGA) were analyzed on MCT4 mRNA (n = 482) and DNA methylation (n = 283) level. The findings on MCT4 expression and DNA methylation in the SLC16A3 promoter were validated in a third cohort (n = 64). Promoter activity assays were conducted in four RCC cell lines. Results: MCT4 protein expression was upregulated (p < 0.0001) in ccRCC and showed significant association with cancer-related death. Upregulation of MCT4 mRNA expression (p < 0.00001) was confirmed in the TCGA cohort. Single CpG sites correlated inversely with mRNA expression and were associated with overall survival in Kaplan-Meier analyses [HR = 0.39; 95% confidence interval (CI), 0.24-0.64; P[log-rank] = 1.23e(-04)]. Promoter activity studies confirmed MCT4 regulation by DNA methylation. The significant correlation between MCT4 protein and gene expression or DNA methylation at single CpG sites was validated in a third cohort. Again, higher methylation at individual CpG sites was associated with prolonged survival [HR = 0.05; 95% CI, 0.01-0.40; P[log-rank] = 6.91e(-05)]. Conclusions: This study identified SLC16A3 promoter DNA methylation as a novel epigenetic mechanism for MCT4 regulation in ccRCC. First evidence of a biological rationale for prognosis and clinical outcome is supported by this specific SLC16A3 promoter DNA methylation.

Differences in promoter DNA methylation and mRNA expression of individual alleles of the HLA class II DQA1 gene

2015 ◽  
Vol 167 (2) ◽  
pp. 147-154 ◽  
Author(s):  
Marta Zajacova ◽  
Anna Kotrbova-Kozak ◽  
Pavel Cepek ◽  
Marie Cerna
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Class Ii ◽  
Hla Class Ii ◽  
Promoter Dna Methylation ◽  
Promoter Dna

Analysis of SNAP25 mRNA expression and promoter DNA methylation in brain areas of Alzheimer’s Disease patients

Neuroscience ◽  
2012 ◽  
Vol 220 ◽  
pp. 41-46 ◽  
Author(s):  
T.K. Furuya ◽  
P.N.O. Silva ◽  
S.L.M. Payão ◽  
P.H.F. Bertolucci ◽  
L.T. Rasmussen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Brain Areas ◽  
Promoter Dna Methylation ◽  
Promoter Dna

HOXA10 mRNA expression and promoter DNA methylation in female pig offspring after in utero estradiol-17β exposure

2013 ◽  
Vol 138 ◽  
pp. 435-444 ◽  
Author(s):  
Veronika L. Pistek ◽  
Rainer W. Fürst ◽  
Heike Kliem ◽  
Stefan Bauersachs ◽  
Heinrich H.D. Meyer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
In Utero ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
Estradiol 17Β

Correlation between TGF-β2/3 promoter DNA methylation and Smad signaling during palatal fusion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin

2021 ◽  
pp. 153537022110122
Author(s):  
Yao Chen ◽  
Xiaozhuan Liu ◽  
Xinxin Liu ◽  
Lingling Cui ◽  
Zhidong He ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cleft Palate ◽  
Promoter Methylation ◽  
Treated Group ◽  
Epigenetic Mechanism ◽  
Control Group ◽  
Smad Signaling ◽  
Promoter Dna Methylation ◽  
Tetrachlorodibenzo P Dioxin ◽  
Promoter Dna

2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) is a persistent organic pollutant that is strongly associated with a number of human diseases and birth defects, including cleft palate. Transforming growth factor (TGF) plays a significant role during mammalian palatogenesis. However, the epigenetic mechanism of transforming growth factors in the process of TCDD-induced cleft palate is unclear. The purpose of this research was to investigate the relationship and potential mechanism between TGF-β2/3 promoter DNA methylation and Smad signaling during TCDD-induced cleft palate. Pregnant C57BL/6N mice were exposed to 64 µg/kg TCDD on gestational day 10 (GD10) to establish the cleft palate model and palatal tissues of embryos were collected on GD13, GD14, and GD15 for subsequent experiments. TGF-β2/3 mRNA expression, TGF-β2/3 promoter methylation, and Smad signaling molecules expression were assessed in the palate of the two groups. The results showed that the incidence of cleft palate was 94.7% in the TCDD-treated group whereas no cleft palate was found in the control group. TCDD-treated group altered specific CpG sites of TGF-β2/3 promoter methylation. Compared to the control group, the proliferation of mouse embryonic palate mesenchymal stromal cells (MEPM), the expressions of TGF-β2/3, p-Smad2, and Smad4 were all reduced, while the expression of Smad7 was significantly increased in the atAR group. Smad signaling was downregulated by TCDD. Therefore, we suggest that TGF-β2/3 promoter methylation and Smad signaling may be involved in TCDD-induced cleft palate formation in fetal mice.

87 IS HOXA10 EXPRESSION REGULATED THROUGH PROMOTER DNA METHYLATION IN THE PIG?

2013 ◽  
Vol 25 (1) ◽  
pp. 191 ◽  
Author(s):  
V. L. Pistek ◽  
R. W. Fürst ◽  
S. Bauersachs ◽  
H. S. Kliem ◽  
H. H. D. Meyer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Early Pregnancy ◽  
In Utero ◽  
Oestrous Cycle ◽  
Control Group ◽  
Postnatal Exposure ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
Estradiol 17Β

In utero and early postnatal exposure to exogenous oestrogens may alter the epigenome, possibly influencing health later in life. The reproductive organs are the main target of oestrogens. Uterine HOXA10 expression and promoter DNA methylation have been shown to be sensitive to endocrine disruptors in rodents. In the endometrium of pigs, in vitro exposure to estradiol-17β resulted in an increase of HOXA10 mRNA and protein expression, and a regulation for HOXA10 has also been shown during early pregnancy. However, it is unclear whether modification in promoter DNA methylation was involved herein. In the present study, we investigated the effect of oral estradiol-17β supplementation to pregnant pigs from Day 0 until delivery (0, 0.05, 10, and 1000 µg kg–1 per day; n = 8–12/group) on HOXA10 expression and promoter DNA methylation in the uterus of prepubertal and the endometrium of postpubertal porcine offspring. In addition, endometrial samples from 2 physiological situations were analyzed, namely the oestrous cycle at Day 0, 3, 6, 12, and 18 (n = 6/day), and early pregnancy at Day 10, 12, and 14 (n = 4/day). Furthermore, different reproductive and nonreproductive tissues from pre- and postpubertal untreated animals were investigated (n = 2/tissue). Gene expression was measured using RT-qPCR. The DNA was first bisulfite converted, amplified by using methylation-sensitive high-resolution melting qPCR, followed by pyrosequencing. Statistical analyses were conducted using one-way ANOVA. In utero estradiol-17β exposure did neither alter HOXA10 expression compared to the control group nor HOXA10 promoter DNA methylation in pre- and postpubertal porcine offspring, respectively. Because the prepubertal group displayed higher HOXA10 mRNA expression than did postpubertal animals, while DNA methylation was lower in the younger animals, a potential role of DNA methylation may be assumed. During the oestrous cycle, HOXA10 expression was significantly regulated (P < 0.001); it was highest at oestrous (Day 0), decreased 2.5-fold by Day 3, and increased again 1.5-fold by Day 6. In early pregnant sows, endometrial HOXA10 transcripts were significantly higher at Day 14 (P = 0.031) compared with nonpregnant controls. In both settings promoter DNA methylation did not change. Regarding HOXA10 expression between different tissues, the DNA methylation at one CpG site was significantly correlated with mRNA expression in prepubertal animals (R2 = 0.582) but not in the adult (R2 = 0.004). We conclude that HOXA10 expression is regulated through other mechanisms than is promoter DNA methylation in adult sows. Still, in prepubertal pigs promoter DNA methylation may influence HOXA10 expression. In utero estradiol-17β exposure did not affect HOXA10 expression and promoter DNA methylation.

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