在三阴性乳腺癌中,通过cis调节机制准昼夜转录程序
bioRxiv : the preprint server for biology
|May 15, 2024
概括
乳腺癌中乱的昼夜钟基因可能是生物标志物. 用CRY2稳定剂和蛋白酶体抑制剂准BMAL1/CLOCK抑制了癌细胞的增殖.
科学领域:
- 癌症生物学 癌症生物学
- 时间生物学 时间生物学
- 基因组学就是基因组学.
背景情况:
- 循环时钟基因与癌症有关,但它们在瘤进展中的作用尚不清楚.
- 乳腺癌中乱的昼夜基因表达可能作为诊断生物标志物.
- 主日间转录因子BMAL1和CLOCK对于转移性中细胞干状 (mMSL) 三重阴性乳腺癌 (TNBC) 细胞增殖至关重要.
研究的目的:
- 为了研究昼夜钟基因在乳腺癌进展中的作用.
- 确定潜在的治疗策略,针对TNBC中的昼夜通路.
- 探索使用昼夜基因表达作为患者分层的生物标志物.
主要方法:
- 利用小分子调节器向加密染色体2 (CRY2) 和蛋白酶体抑制剂.
- 对药物治疗的mMSL TNBC细胞进行了omics分析.
- 雇佣了大量的并行记者测试来定义 cis-regulatory element (CRE) 的特征.
主要成果:
- 一种CRY2稳定剂和蛋白酶体抑制剂的组合抑制了mMSL TNBC细胞中的昼夜循环基因.
- 奥米克斯数据表明,CREs中的转录因子结合位 (TFBS) 调解了这种抑制.
- 确定了由药物组合抑制的特定CRE特征.
结论:
- 乳腺癌中乱的昼夜基因表达具有作为生物标记物的潜力.
- 通过CRY2稳定剂和蛋白酶体抑制剂向BMAL1和CLOCK活性,对TNBC显示出治疗的希望.
- 调节 cis-regulatory 程序为设计未定义驱动器的癌症疗法提供了一个新的范式,比如 TNBC.
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