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Genome-scale CRISPR screening for potential targets of ginsenoside compound K

机译:基因组规模克切普尔筛选人参皂苷类化合物K的潜在靶

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Ginsenosides exhibit a large variety of biological activities in maintaining physical health; however, the molecule underpinnings underlining these biological activities remain to be defined. Here, we took a cellular condition that compound K (CK) induces autophagic cell death in HeLa cells, and setup a high-throughput genetic screening using CRISPR technology. We have identified a number of CK-resistant and CK-sensitive genes, and further validated PMAIP1 as a CK-resistant gene and WASH1 as a CK-sensitive gene. Compound K treatment reduces the expression of WASH1, which further accelerates the autophagic cell death, highlighting WASH1 as an interesting downstream mediator of CK effects. Overall, our study offers an easy-to-adopt platform to study the functional mediators of ginsenosides, and provides a candidate list of genes that are potential targets of CK.
机译:人参皂苷在维持身体健康方面表现出各种各样的生物活性;然而,仍然定义下划线这些生物活性的分子内衬里。在这里,我们采取了一种细胞条件,即化合物K(CK)在HeLa细胞中诱导自噬细胞死亡,并使用CRISPR技术设置高通量遗传筛查。我们已经鉴定了许多CK抗性和CK敏感的基因,以及进一步验证的P​​MAIP1作为CK抗性基因和WASK1作为CK敏感基因。化合物K治疗减少了Wash1的表达,进一步加速了自噬细胞死亡,突出了Wash1作为CK效应的有趣下游介质。总体而言,我们的研究提供了一种易于采用的平台来研究人参皂苷的功能介质,并提供候选基因列表,这是CK的潜在目标。

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