Regulatory Single Nucleotide Polymorphism Increases <b><i>TERT</i></b> Promoter Activity in Thyroid Carcinoma Cells
Regulatory Single Nucleotide Polymorphism Increases <b><i>TERT</i></b> Promoter Activity in Thyroid Carcinoma Cells
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调节性单核苷酸多态性增加甲状腺癌细胞中 <b><i>TERT</i></b> 启动子活性
DOI：
10.1159/000509752
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发表时间：
2020
期刊：
影响因子：
5
通讯作者：
Kamma Hiroshi
中科院分区：
文献类型：
--
作者：
Hirokawa Tatsuya;Arimasu Yuu;Chiba Tomohiro;Nakazato Yoko;Fujiwara Masachika;Kamma Hiroshi
背景/目的：端粒酶逆转录酶（TERT）启动子具有一个调节性单核苷酸多态性（rSNP）rs 2853669，偶尔会出现C228 T和C250 T点突变。虽然C228 T和C250 T已被很好地检测到增加TERT启动子活性，并被认为是甲状腺癌的危险因素，但rs 2853669的意义尚未得到很好的研究。材料：8株甲状腺癌细胞系中7株含有rs 2853669基因，5株含有C228 T基因，1株含有C250 T基因。结果：3株同时含有rs 2853669和C228 T基因的甲状腺乳头状癌细胞系，其TERTmRNA表达均高于其他细胞系。与此相反，未分化甲状腺癌细胞系表现出依赖于rs 2853669、C228 T和C250 T组合的可变TERTmRNA表达。比较rs 2853669、C228 T和C250 T对甲状腺癌中TERT启动子活性的影响的荧光素酶测定显示，rs 2853669以及C228 T增加启动子活性，并且rs 2853669和C228 T的组合比单独的C228 T更强烈地增加启动子活性。我们的结论是，在甲状腺癌中，TERT启动子内rs 2853669的存在可能与C228 T突变一样重要。
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 increaseTERTpromoter 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 onTERTpromoter 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 higherTERTmRNA expression on real-time PCR than the other cell lines. Anaplastic thyroid carcinoma cell lines, in contrast, showed variableTERTmRNA expression depending on the combination of rs2853669, C228T, and C250T. Luciferase assays, performed to compare the influences of rs2853669, C228T, and C250T onTERTpromoter 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 theTERTpromoter could be as significant as the C228T mutation in thyroid carcinoma.
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影响因子：
4.5
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