The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR-Cas9 screen

Certain cancers, such as ovarian clear cell carcinoma (OCCC), display high levels of genetic variation between patients, confounding the development of effective therapies. In order to identify novel genes critical to OCCC growth, we employed the pooled genome-scale CRISPR Knock-Out (GeCKO) v2 CRISPR-Cas9 knockout screening system using the OCCC cell line JHOC5, as well as the T-antigen immortalized normal ovarian surface epithelium cell line OSE3 as a negative control. We identified the gene encoding DHX38/PRP16, an ATP-dependent RNA helicase involved in splicing, as critical for the growth and tumorigenesis of OCCC; DHX38 knockdown in OCCC cells, but not normal cells, induces apoptosis and impairs OCCC tumorigenesis in a mouse model. Our results suggest that DHX38/PRP16 may play a role in OCCC tumorigenesis, and can be regarded as a promising therapeutic target. Overall design: Genome-wide CRISPR/Cas9 screen of JHOC5 (ovarian cancer cell) and OSE3 (normal ovarian epithelial cell) using the GeCKO v2 pooled sgRNA library.