AURKB和PI3K/AKT/mTOR通路汇聚在一起,以调节TERT表达
Grace Lim1, Althea Bastian1,2, Saskia Fung1,3
1Cancer Genetics Laboratory, Kolling Institute, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney & Northern Sydney Local Health District, St Leonards, NSW, Australia.
TERT促进子突变驱动癌症的进展,可以被向. 新的研究揭示了Aurora kinase B和TRIM28调节这些突变,为TERT促进器突变驱动的癌症提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 保持端粒长度对于癌症进展至关重要.
- 由于其瘤特异性,TERT促进子突变 (TERTp MUT) 是不良的预后标志物和潜在的治疗点.
研究的目的:
- 为了确定调节TERT促进子突变 (TERTp MUT) 活动的新途径.
- 探索TERT促进子突变作为治疗瘤甲状腺癌的治疗标.
主要方法:
- 使用CRISPR-Cas9生成了SW1736 TERT/LUC细胞,这些细胞具有TERT促进子突变下游的光酶记者.
- 一个218酶抑制剂库被选,以确定TERT促进体突变活性的调节者.
- 在甲状腺癌模型中使用了定量PCR,免疫沉 (IP) 和染色素IP.
主要成果:
- 鉴定出PI3K/AKT/mTOR1信号传导和光激酶B (AURKB) 是TERT促进体突变活性的共同调节者,超出了MAPK信号传导.
- 不同的因素调节野生类型和突变的TERT促销者.
- 通过REST,AURKB被TRIM28.8.招募到TERT促进子突变中.
结论:
- TRIM28被强调为TERT促进子突变驱动的癌症的潜在治疗标.
- 了解TERT促进者的独特调节机制为癌症治疗提供了新的途径.
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