Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) of folate metabolism genes can influence the methylation of tumour suppressor genes, thereby potentially impacting on tumour behaviour. To investigate whether such polymorphisms influence lung cancer survival, we genotyped 14 nsSNPs mapping to methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR); DNA methyltransferase (DNMT2), methylenetetrahydrofolate dehydrogenase (MTHFD1) and methenyltetrahydrofolate synthetase (MTHFS) in 619 Caucasian women with incident disease, 465 with non-small cell (NSCLC) and 154 with small cell lung cancer (SCLC). The most significant association detected was with MTHFS Thr202Ala, with carriers of variant alleles having a worse prognosis (hazard ratio (HR)=1.49; 95% confidence interval: 1.14-1.94). Associations were also detected between overall survival (OS) in SCLC and homozygosity for MTHFR 222Val (HR=1.92; 1.03-3.58) and between OS from NSCLC and MTRR 175Leu carrier status (HR=1.36; 1.06-1.75). While there is evidence that variation in the folate metabolism genes may influence prognosis from lung cancer, current data are insufficiently robust to distinguish individual patient outcome.
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PMID:Prognostic significance of folate metabolism polymorphisms for lung cancer. 1753 96

BACKGROUND Non-small cell lung cancer (NSCLC) accounts for about 85% of all types of lung cancer. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is involved in DNA methylation, and DNA methylation is related to tumorigenesis. The role of MTHFD1 in NSCLC was examined in our study. MATERIAL AND METHODS The correlation between the expression of MTHFD1 and the clinicopathological features of patients diagnosed with lung cancer was investigated using the chi-square test. The viability and apoptosis of NCI-H1299 cells was respectively detected using cell counting kit-8 and flow cytometry assays. The expression levels of MTHFD1, apoptosis-related factors and DNA methyltransferase-related factors were assessed by quantitative real-time PCR (qRT-PCR) and western blot assays. RESULTS We found that MTHFD1 expression in the tumor tissues and cells was higher than that of adjacent normal tissues and cells. The survival time of patients with high MTHFD1 expression was shorter than those with low MTHFD1 expression. The expression level of MTHFD1 was related to tumor size, TNM stage, histologic grade, and metastasis, but not linked to gender and age. Besides, si-MTHFD1 significantly decreased the viability of cells in a time-dependent manner, and increased cell apoptosis. When cells were transfected with MTHFD1-siRNA, the levels of surviving and B-cell lymphoma-2 (Bcl-2) were attenuated, while p53 and Bcl-2 associated X protein (Bax) levels were enhanced. Moreover, si-MTHFD1 markedly downregulated the expression levels of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b. CONCLUSIONS Collectively, our results proved that MTHFD1 silencing obviously reduced the proliferation and enhanced the apoptosis of NSCLC via suppressing DNA methylation.
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PMID:Methylenetetrahydrofolate Dehydrogenase 1 Silencing Expedites the Apoptosis of Non-Small Cell Lung Cancer Cells via Modulating DNA Methylation. 3034 10