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Niknam, Maryam, Naghibalhossaini, Fakhraddin, Zamani, Mozhdeh, Hosseini, Seyed Vahid, Mokarram, Pooneh. (1403). The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran. , 13(2), 89-102. doi: 10.22099/mbrc.2023.48009.1850
Maryam Niknam; Fakhraddin Naghibalhossaini; Mozhdeh Zamani; Seyed Vahid Hosseini; Pooneh Mokarram. "The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran". , 13, 2, 1403, 89-102. doi: 10.22099/mbrc.2023.48009.1850
Niknam, Maryam, Naghibalhossaini, Fakhraddin, Zamani, Mozhdeh, Hosseini, Seyed Vahid, Mokarram, Pooneh. (1403). 'The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran', , 13(2), pp. 89-102. doi: 10.22099/mbrc.2023.48009.1850
Niknam, Maryam, Naghibalhossaini, Fakhraddin, Zamani, Mozhdeh, Hosseini, Seyed Vahid, Mokarram, Pooneh. The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran. , 1403; 13(2): 89-102. doi: 10.22099/mbrc.2023.48009.1850

The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran

Molecular Biology Research Communications
دوره 13، شماره 2، 2024، صفحه 89-102    اصل مقاله (916.6 K)
نوع مقاله: Original article
شناسه دیجیتال (DOI): 10.22099/mbrc.2023.48009.1850
نویسندگان
Maryam Niknam1؛ Fakhraddin Naghibalhossaini1، 2؛ Mozhdeh Zamani1، 3؛ Seyed Vahid Hosseini4؛ Pooneh Mokarram* 5
1Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran
2Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran
3Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5Autophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
چکیده
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.
کلیدواژه‌ها
Thymidylate synthase؛ Methylation؛ DNA methyltransferase؛ Histone deacetylase؛ Colorectal cancer
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