CRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer.
iScience
; 27(5): 109676, 2024 May 17.
Article
em En
| MEDLINE
| ID: mdl-38665208
ABSTRACT
Growing evidences indicate that RNA-binding proteins (RBPs) play critical roles in regulating the RNA splicing, polyadenylation, stability, localization, translation, and turnover. Abnormal expression of RBPs can promote tumorigenesis. Here, we performed a CRISPR screen using an RBP pooled CRISPR knockout library and identified 27 potential RBPs with role in supporting colorectal cancer (CRC) survival. We found that the deletion/depletion of INTS3 triggered apoptosis in CRC. The in vitro experiments and RNA sequencing revealed that INTS3 destabilized pro-apoptotic gene transcripts and contributed to the survival of CRC cells. INTS3 loss delayed CRC cells growth in vivo. Furthermore, delivery of DOTAP/cholesterol-mshINTS3 nanoparticles inhibited CRC tumor growth. Collectively, our work highlights the role of INTS3 in supporting CRC survival and provides several novel therapeutic targets for treatment.
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
IScience
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China