biostudies-literatureWang ZMinistry of Science and Technology of the People&apos;s Republic of ChinaNational Natural Science Foundation of China109676https://www.ebi.ac.uk/biostudies/studies/S-EPMC11043890biostudies-literatureUnknown27(5)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 <i>in vitro</i> 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 <i>in vivo</i>. Furthermore, delivery of DOTAP/cholesterol-mshINTS3 nanoparticles inhibited CRC tumor growth. Collectively,iScienceCRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer.PMC1104389032200652821731762020YFA0803500Li PZeng XLiu SZhang LHe QZhu PYang YGuo JChen ZZhao QZhai JWang XZhang CWang ZfalseCRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer.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 <i>in vitro</i> 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 <i>in vivo</i>. Furthermore, delivery of DOTAP/cholesterol-mshINTS3 nanoparticles inhibited CRC tumor growth. Collectively,2024-01-01T00:00:00Z2024 May2026-06-03T03:57:26.114Z2026-04-24T03:09:31.042ZS-EPMC110438903866520810.1016/j.isci.2024.109676