Loss of ZNF587B and SULF1 contributed to cisplatin resistance in ovarian cancer cell lines based on Genome-scale CRISPR/Cas9 screening

[摘要] Ovarian cancer is one of the most lethal malignancies of the female reproductive system. Platinum-resistance is the major obstacle in the successful treatment of ovarian cancer. Previous studies largely failed to identify the key genes associated with platinum-resistance by using candidate genes testing, bioinformatic analysis and GWAS method. The aim of the study was to utilize the whole human Genome-scale CRISPR-Cas9 knockout (GeCKO) library to screen for novel genes involved in cisplatin resistance in ovarian cancer cell lines. The GeCKO library targeted 19052 genes with 122417 unique guide sequences. Six candidate genes had been screened out including one previously validated gene SULF1 and five novel genes ZNF587B, TADA1, SEMA4G, POTEC and USP17L20. After validated by CCK-8 and RT-PCR analysis, two genes (ZNF587B and SULF1) were discovered to be involved in cisplatin resistance. ZNF587B may serve as a new biomarker for predicting cisplatin resistance.

[学科分类] 肿瘤学

[关键词] CRISPR/Cas 9;ovarian cancer;platinum;SULF1;ZNF587B