A genome-scale CRISPR/Cas9 knockout screening reveals SH3D21 as a sensitizer for gemcitabine
A genome-scale CRISPR/Cas9 knockout screening reveals SH3D21 as a sensitizer for gemcitabine
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DOI：
10.1038/s41598-019-55893-2
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发表时间：
2019-12-16
影响因子：
4.6
通讯作者：
Aburatani, Hiroyuki
中科院分区：
文献类型：
--
作者：
Masoudi, Mohammad;Seki, Motoaki;Aburatani, Hiroyuki
吉西他滨为2‘，2’-二氟-2‘-脱氧胞苷，用于治疗包括胰腺癌在内的多种实体肿瘤。吉西他滨摄入后，通过膜核苷转运蛋白转移到细胞内。一旦进入细胞，它就会转化为吉西他滨三磷酸，然后并入DNA链，在那里它会抑制DNA复制，从而抑制细胞周期停滞和细胞凋亡。目前，吉西他滨是治疗胰腺癌的标准药物，尽管它被广泛使用，但其疗效中等。在这项研究中，我们对胰腺癌细胞系Panc1进行了基因组规模的CRISPR/Cas9基因敲除筛选，以探索与吉西他滨疗效相关的重要基因。我们发现SH3D21是一种新的吉西他滨增敏剂，提示它可能成为提高吉西他滨治疗胰腺癌疗效的治疗靶点。
Gemcitabine, 2',2'-difluoro-2'-deoxycytidine, is used as a pro-drug in treatment of variety of solid tumour cancers including pancreatic cancer. After intake, gemcitabine is transferred to the cells by the membrane nucleoside transporter proteins. Once inside the cells, it is converted to gemcitabine triphosphate followed by incorporation into DNA chains where it causes inhibition of DNA replication and thereby cell cycle arrest and apoptosis. Currently gemcitabine is the standard drug for treatment of pancreatic cancer and despite its widespread use its effect is moderate. In this study, we performed a genome-scale CRISPR/Cas9 knockout screening on pancreatic cancer cell line Panc1 to explore the genes that are important for gemcitabine efficacy. We found SH3D21 as a novel gemcitabine sensitizer implying it may act as a therapeutic target for improvement of gemcitabine efficacy in treatment of pancreatic cancer.