CRISPR-Cas9蛋白激酶文库筛选胰腺癌多药耐药共同靶点的价值

doi:10.3969/j.issn.1671-7171.2024.12.002

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Abstract 【Objective】To analyze the value of CRISPR-Cas9 protein kinase library in screening common targets for multi-drug resistance in pancreatic cancer. 【Methods】 PDAC cell line TB32047 derived from KPC mouse model was transfected with lentivirus and treated with oxaliplatin, fluorouracil and ilictecan at IC90 concentration for 3 weeks. Next generation sequencing and MAGeCK VISPR analysis were performed to identify candidate genes through CRISPR-Cas9 function loss screening. The synergistic effect of cyclin-dependent kinase 7 (CDK7) depletion or targeted inhibition with FOLFIRINOX chemotherapy for pancreatic cancer was examined by MTT, flow cytometry, and colony formation assay.【Results】CDK7 ranked high in the screening of three chemotherapy drugs, and was a common target of multi-drug resistance in pancreatic cancer. After completely knocking out CDK7 with CRISPR-Cas9 or inhibiting CDK7 expression with THZ1,pancreatic cancer cell proliferation was slowed down, the cell cycle was blocked and apoptosis increased, while colony-forming ability decreased, and together with FOLFIRINOX, they promoted apoptosis of pancreatic cancer cells. 【Conclusion】CDK7 is a common target of multi-drug resistance in pancreatic cancer, and CDK7 is a new target to overcome chemotherapy resistance in pancreatic cancer.

Key words： Pancreatic Neoplasms Protein Kinases Drug Resistance,Multiple Gene Library

Received: 08 October 2024

PACS:

R735.9

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	Articles by authors
	ZENG Siyuan
	LAN Bin
	WANG Huiling
	et al

Cite this article:

ZENG Siyuan,LAN Bin,WANG Huiling, et al. Value of CRISPR-Cas9 Protein Kinase Libraries in Screening Common Targets for Multidrug Resistance in Pancreatic Cancer[J]. JOURNAL OF CLINICAL RESEARCH, 2024, 41(12): 1828-1832.

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http://journal07.magtech.org.cn/yxlcyj/EN/10.3969/j.issn.1671-7171.2024.12.002 OR http://journal07.magtech.org.cn/yxlcyj/EN/Y2024/V41/I12/1828

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