调控单核苷酸多态性可增强甲状腺癌细胞中端粒酶逆转录酶启动子活性。

Regulatory Single Nucleotide Polymorphism Increases TERT Promoter Activity in Thyroid Carcinoma Cells.

机构信息

Department of Pathology, School of Medicine, Kyorin University, Mitaka, Japan.

Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.

出版信息

Pathobiology. 2020;87(6):338-344. doi: 10.1159/000509752. Epub 2020 Nov 23.

DOI:10.1159/000509752

PMID:33227798

Abstract

BACKGROUND/AIM: The telomerase reverse transcriptase (TERT) promoter has a regulatory single nucleotide polymorphism (rSNP), rs2853669, and occasionally shows point mutations C228T and C250T. Although C228T and C250T have been well examined to increase TERT promoter activity and are known as risk factors for thyroid carcinoma, the significance of rs2853669 has not been well investigated. This study aimed to clarify the influence of rs2853669 on TERT promoter activity in thyroid carcinoma cells.

MATERIALS

Seven of 8 examined thyroid cell lines had rs2853669, 5 had C228T, and 1 had C250T.

RESULTS

Three papillary thyroid carcinoma cell lines, harboring both rs2853669 and C228T, showed higher TERT mRNA expression on real-time PCR than the other cell lines. Anaplastic thyroid carcinoma cell lines, in contrast, showed variable TERT mRNA expression depending on the combination of rs2853669, C228T, and C250T. Luciferase assays, performed to compare the influences of rs2853669, C228T, and C250T on TERT promoter activity in thyroid carcinoma, showed that rs2853669, as well as C228T, increased the promoter activity, and the combination of rs2853669 and C228T increased the promoter activity even more strongly than C228T alone.

CONCLUSION

We conclude that the presence of rs2853669 within the TERT promoter could be as significant as the C228T mutation in thyroid carcinoma.

摘要

背景/目的：端粒酶逆转录酶（TERT）启动子具有调节性单核苷酸多态性（rSNP）rs2853669，偶尔会出现点突变 C228T 和 C250T。尽管 C228T 和 C250T 已被充分研究以增加 TERT 启动子活性，并被认为是甲状腺癌的危险因素，但 rs2853669 的意义尚未得到充分研究。本研究旨在阐明 rs2853669 对甲状腺癌细胞中 TERT 启动子活性的影响。

材料

在 8 种检测的甲状腺细胞系中，有 7 种存在 rs2853669，5 种存在 C228T，1 种存在 C250T。

结果

三种甲状腺乳头状癌细胞系同时存在 rs2853669 和 C228T，实时 PCR 显示 TERT mRNA 表达高于其他细胞系。相反，间变性甲状腺癌细胞系的 TERT mRNA 表达根据 rs2853669、C228T 和 C250T 的组合而有所不同。进行荧光素酶测定以比较 rs2853669、C228T 和 C250T 对甲状腺癌 TERT 启动子活性的影响，结果表明 rs2853669 与 C228T 一样，增加了启动子活性，rs2853669 与 C228T 的组合比单独的 C228T 更强烈地增加了启动子活性。