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由BRAF诱导的EHF表达影响了侵袭性乳头甲状腺癌中的TERT
Yiyi Xu1, Jiwei Gao1,2, Na Wang3
1Department of Oncology-Pathology, Karolinska Institutet, Stockholm SE-171 64, Sweden.
The Journal of clinical endocrinology and metabolism
|August 25, 2024
概括
通过增加TERT表达,ETS转录因子EHF恶化了皮肤状甲状腺癌 (PTC) 的预后,特别是当BRAFV600E和TERT促进因子突变存在时. 这一发现为PTC提供了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 乳头甲状腺癌 (PTC) 的预后受到 BRAFV600E 和 TERT 促成因子突变的协同影响.
- 这种相互作用被认为涉及MAPK激活,导致ETS转录因子上调,以突变的TERT促进体为目标.
研究的目的:
- 研究ETS因子在PTC中的作用,重点关注它们与临床特征,BRAFV600E和TERT促进子突变的关系.
- 阐明ETS因素EHF在PTC进展和TERT监管中的具体参与.
主要方法:
- 对癌症基因组图谱 (TCGA) PTC队列 (n=399) 和局部队列 (n=93) 中28个ETS因子的转录组数据分析.
- 在体外实验,包括过度表达和敲击研究,以评估EHF在BRAFV600E和TERT表达中的调节作用.
- 染色体免疫沉 (ChIP) 和定量PCR (qPCR) 用于评估EHF与TERT促进体的结合.
主要成果:
- 在两个队列中,EHF被确定为与不良临床特征,BRAFV600E和TERT促进体突变/表达相关的关键ETS因子.
- 高EHF表达与BRAFV600E突变PTC中较短的无病生存时间相关.
- 同时出现的BRAFV600E,TERT促进子突变和高EHF表达导致了最差的预后.
- 在具有同时BRAFV600E和TERT促进子突变的细胞中,EHF过度表达增加了TERT表达; BRAF抑制减少了EHF和TERT.
- 奇普-qPCR建议EHF与突变的TERT促进体结合.
结论:
- ETS转录因子EHF与PTC的预后不佳有关.
- BRAF-V600E可能对EHF进行升级调节,从而在TERT促进剂突变的PTC细胞中增强TERT表达.
- 在PTC中,EHF代表了一个潜在的治疗标,特别是在具有特定遗传改变的瘤中.
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