» Articles » PMID: 35723366

CRISPR/Cas9 Screening for Identification of Genes Required for the Growth of Ovarian Clear Cell Carcinoma Cells

Overview
Publisher MDPI
Specialty Molecular Biology
Date 2022 Jun 20
PMID 35723366
Authors
Affiliations
Soon will be listed here.
Abstract

Epithelial ovarian cancer is classified into four major histological subtypes: serous, clear cell, endometrioid and mucinous. Ovarian clear cell carcinoma (OCCC) responds poorly to conventional chemotherapies and shows poor prognosis. Thus, there is a need to develop new drugs for the treatment of OCCC. In this study, we performed CRISPR/Cas9 screens against OCCC cell lines and identified candidate genes important for their proliferation. We found that quite different genes are required for the growth of ARID1A and PIK3CA mutant and wild-type OCCC cell lines, respectively. Furthermore, we found that the epigenetic regulator KDM2A and the translation regulator PAIP1 may play important roles in the growth of ARID1A and PIK3CA mutant, but not wild-type, OCCC cells. The results of our CRISPR/Cas9 screening may be useful in elucidating the molecular mechanism of OCCC tumorigenesis and in developing OCCC-targeted drugs.

References
1.
Cheung H, Cowley G, Weir B, Boehm J, Rusin S, Scott J . Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer. Proc Natl Acad Sci U S A. 2011; 108(30):12372-7. PMC: 3145679. DOI: 10.1073/pnas.1109363108. View

2.
Guan H, Li N, Wang X, Shan X, Li Z, Lin Z . Role of Paip1 on angiogenesis and invasion in pancreatic cancer. Exp Cell Res. 2019; 376(2):198-209. DOI: 10.1016/j.yexcr.2019.01.017. View

3.
Hart T, Tong A, Chan K, van Leeuwen J, Seetharaman A, Aregger M . Evaluation and Design of Genome-Wide CRISPR/SpCas9 Knockout Screens. G3 (Bethesda). 2017; 7(8):2719-2727. PMC: 5555476. DOI: 10.1534/g3.117.041277. View

4.
Mizuno M, Kikkawa F, Shibata K, Kajiyama H, Ino K, Kawai M . Long-term follow-up and prognostic factor analysis in clear cell adenocarcinoma of the ovary. J Surg Oncol. 2006; 94(2):138-43. DOI: 10.1002/jso.20251. View

5.
Kwok A, Wong O, Wong E, Tsun O, Chan K, Cheung A . Caution over use of ES2 as a model of ovarian clear cell carcinoma. J Clin Pathol. 2014; 67(10):921-2. DOI: 10.1136/jclinpath-2014-202430. View