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The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR-Cas9 screen.
Cona, Brandon; Hayashi, Tomoatsu; Yamada, Ai; Shimizu, Naomi; Yokota, Naoko; Nakato, Ryuichiro; Shirahige, Katsuhiko; Akiyama, Tetsu.
Affiliation
  • Cona B; Laboratory of Molecular and Genetic Information, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
  • Hayashi T; Laboratory of Molecular and Genetic Information, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
  • Yamada A; Laboratory of Molecular and Genetic Information, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
  • Shimizu N; Laboratory of Molecular and Genetic Information, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
  • Yokota N; Laboratory of Computational Genetics, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
  • Nakato R; Laboratory of Computational Genetics, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
  • Shirahige K; Laboratory of Genome Structure and Function, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
  • Akiyama T; Laboratory of Molecular and Genetic Information, Institute of Quantitative Biosciences, The University of Tokyo, Japan.
FEBS Open Bio ; 12(3): 582-593, 2022 03.
Article in En | MEDLINE | ID: mdl-34965029
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Adenocarcinoma, Clear Cell / RNA Splicing Factors Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: FEBS Open Bio Year: 2022 Document type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Adenocarcinoma, Clear Cell / RNA Splicing Factors Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: FEBS Open Bio Year: 2022 Document type: Article Affiliation country: Japan