Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences Kerman University of Medical Sciences, Kerman, Iran.
Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Front Endocrinol (Lausanne). 2023 Jul 25;14:1130794. doi: 10.3389/fendo.2023.1130794. eCollection 2023.
Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients.
OCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis.
Further TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, =0.001) and P16 (OR=5.65, <0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, <0.001) and H4K16 (OR=6.03, <0.001) acetylation.
The current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.
癌症的发病率取决于多种因素，例如接触杀虫剂导致的表观遗传改变。本研究旨在调查有机氯农药 (OCPs) 对甲状腺结节中三个肿瘤抑制基因启动子甲基化和四种组蛋白修饰的影响，共纳入 61 例甲状腺乳头状癌 (PTC) 和 70 例良性甲状腺结节 (BTN) 患者。
采用气相色谱法检测 OCPs。利用巢式甲基化特异性 PCR (MSP) 检测 TSHR、ATM 和 P16 基因的启动子甲基化，通过 Western blot 分析检测组蛋白赖氨酸乙酰化 (H3K9、H4K16 和 H3K18) 和赖氨酸甲基化 (H4K20)。
与 BTN 相比，PTC 中 TSHR 的甲基化程度更高，P16 的甲基化程度更低。PTC 和 BTN 组之间 ATM 甲基化没有显著差异。此外，OCP 显著增加了 TSHR (OR=3.98, =0.001) 和 P16 (OR=5.65, <0.001) 甲基化的比值，而混杂因素降低了 2,4-DDE 和 4,4-DDT 对 ATM 甲基化的影响。与 BTN 相比，PTC 样本中 H4K20 呈低甲基化，H3K9、H4K16 和 H3K18 呈低乙酰化(<0.001)。此外，OCP 显著降低了 H3K9 (OR=3.68, <0.001) 和 H4K16 (OR=6.03, <0.001) 的乙酰化比值。
本研究表明，OCPs 可能通过 TSHR 启动子过度甲基化和 H3K9 和 H4K16 乙酰化降低促进 PTC 进展。此外，在 PTC 患者中，评估 TSHR 启动子甲基化和 H3K9 和 H4K16 的乙酰化可能具有预测价值。
