High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming.
High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming.
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通过靶向转录重编程发现抗癌药物的高通量策略。
DOI：
10.3389/fonc.2021.762023
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发表时间：
2021
影响因子：
4.7
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Huang L;Yi X;Yu X;Wang Y;Zhang C;Qin L;Guo D;Zhou S;Zhang G;Deng Y;Bao X;Wang D
转录重编程有助于癌症的进展和复发。然而，肿瘤转录重编程机制的不清楚使得有效药物的开发变得困难，而基因表达标签有助于将遗传信息与药物治疗联系起来。到目前为止，有两种基于基因表达特征的高通量药物发现方法：L1000，测量978个“地标”基因的mRNA转录丰度，以及基于高通量测序的高通量筛选（HTS 2）;它们适合通过靶向转录重编程进行抗癌药物发现。L1000使用连接介导的扩增和与Luminex微珠的杂交，并通过检测微珠颜色和藻红蛋白信号的荧光强度来突出显示基因表达变化。HTS 2利用RNA介导的寡核苷酸退火，选择和连接，高通量测序，通过直接测量基因序列来定量基因表达变化。本文综述了L1000和HTS 2的技术原理和应用，并讨论了它们在抗癌药物发现中的优势和局限性。
Transcriptional reprogramming contributes to the progression and recurrence of cancer. However, the poorly elucidated mechanisms of transcriptional reprogramming in tumors make the development of effective drugs difficult, and gene expression signature is helpful for connecting genetic information and pharmacologic treatment. So far, there are two gene-expression signature-based high-throughput drug discovery approaches: L1000, which measures the mRNA transcript abundance of 978 “landmark” genes, and high-throughput sequencing-based high-throughput screening (HTS2); they are suitable for anticancer drug discovery by targeting transcriptional reprogramming. L1000 uses ligation-mediated amplification and hybridization to Luminex beads and highlights gene expression changes by detecting bead colors and fluorescence intensity of phycoerythrin signal. HTS2 takes advantage of RNA-mediated oligonucleotide annealing, selection, and ligation, high throughput sequencing, to quantify gene expression changes by directly measuring gene sequences. This article summarizes technological principles and applications of L1000 and HTS2, and discusses their advantages and limitations in anticancer drug discovery.
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