The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR-Cas9 screen.
Brandon ConaTomoatsu HayashiAi YamadaNaomi ShimizuNaoko YokotaRyuichiro NakatoKatsuhiko ShirahigeTetsu AkiyamaPublished in: FEBS open bio (2022)
Certain cancers, such as ovarian clear cell carcinoma (OCCC), display high levels of genetic variation between patients, making it difficult to develop effective therapies. In order to identify novel genes critical to OCCC growth, we carried out a comprehensive CRISPR-Cas9 knockout screen against cell growth using an OCCC cell line and a normal ovarian surface epithelium cell line. 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/PRP16 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 could potentially be a promising therapeutic target.
Keyphrases
- crispr cas
- induced apoptosis
- platelet rich plasma
- genome editing
- mouse model
- cell cycle arrest
- end stage renal disease
- chronic kidney disease
- genome wide
- high throughput
- ejection fraction
- newly diagnosed
- cell death
- peritoneal dialysis
- genome wide identification
- signaling pathway
- transcription factor
- patient reported outcomes