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

Qianying Ouyang; Yujie Liu; Jieqiong Tan; Jie Li; Dawei Yang; Feiyue Zeng; Weihua Huang; Yi Kong; Zhaoqian Liu; Honghao Zhou; Yingzi Liu

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

Am J Cancer Res. 2019 May 1;9(5):988-998. eCollection 2019.

Authors

Qianying Ouyang^{1

2

3

4}, Yujie Liu^{1

2

3

4}, Jieqiong Tan⁵, Jie Li⁵, Dawei Yang⁵, Feiyue Zeng⁶, Weihua Huang^{1

2

3

4}, Yi Kong⁷, Zhaoqian Liu^{1

2

3

4}, Honghao Zhou^{1

2

3

4}, Yingzi Liu^{1

2

3

4}

Affiliations

¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University 87 Xiangya Road, Changsha 410008, Hunan, P. R. China.
² Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics 110 Xiangya Road, Changsha 410078, Hunan, P. R. China.
³ Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education 110 Xiangya Road, Changsha 410078, Hunan, P. R. China.
⁴ National Clinical Research Center for Geriatric Disorders 87 Xiangya Road, Changsha 410008, Hunan, P. R. China.
⁵ Center for Medical Genetics and School of Life Science, Central South University Changsha 410008, Hunan, P. R. China.
⁶ Department of Radiology, Xiangya Hospital, Central South University Changsha 410008, Hunan, P. R. China.
⁷ Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School of Central South University Changsha 410013, Hunan, P. R. China.

PMID: 31218106
PMCID: PMC6556596

Abstract

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.

Keywords: CRISPR/Cas 9; SULF1; ZNF587B; ovarian cancer; platinum.