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Molecular Biology Research Communications، جلد ۱۳، شماره ۲، صفحات ۸۹-۱۰۲
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عنوان انگلیسی The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran
چکیده انگلیسی مقاله To investigate the effects of thymidylate synthase (TS) 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of TS 3'UTR genotype with promoter methylation of hTERT, hMLH1, MSH2, MMP2, CDH1, p14, p16, and p21 genes in CRC patients. The polymorphism of TS 3′UTR was evaluated through mutagenically specific PCR. The genes promoter methylation was determined using methylation-specific PCR. For 10 patients, the gene expression profile of epigenetic regulating enzymes, histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), was also examined in both tumor and normal adjacent tissues by quantitative real time PCR. There was a significant association between the hMLH1 methylation and age of patients (P= 0.039) and also between MSH2 methylation and tumor site (P= 0.036). There was insignificant association between gene-specific methylation and TS 3′UTR genotype. However, all polymorphic genotypes of TS were associated with higher methylation of hMLH1 and CDH1 and lower methylation of MSH2. The -6bp/+6bp (heterozygous mutant) and [-6bp/+6bp, +6bp/+6bp] (homozygous mutant) genotypes resulted in higher methylation of p16, and -6bp/+6bp and [-6bp/+6bp, +6bp/+6bp] genotypes were correlated with lower methylation of MMP2. The overexpression of epigenetic enzymes, HDACs and DNMTs, was also demonstrated. There was no association between DNMTs transcript levels and gene-specific hypermethylation. The polymorphic TS genotypes, especially -6bp/+6bp, could affect methylation frequencies of studied genes. Moreover, promoter methylation status was not dependent on DNMTs gene expression. Large sample size studies may contribute to validate these findings.
کلیدواژه‌های انگلیسی مقاله Thymidylate synthase, Methylation, DNA methyltransferase, Histone deacetylase, Colorectal cancer
نویسندگان مقاله Maryam Niknam |
Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran

Fakhraddin Naghibalhossaini |
Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran

Mozhdeh Zamani |
Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran

Seyed Vahid Hosseini |
Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Pooneh Mokarram |
Autophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

نشانی اینترنتی https://mbrc.shirazu.ac.ir/article_7380_7defca20cd3df3f27f374ac1b7e3830b.pdf
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