2. Academic Validation
  3. CRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer

CRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer

  • iScience. 2024 Apr 6;27(5):109676. doi: 10.1016/j.isci.2024.109676.
Zhiwei Wang 1,  Cheng Zhang 1,  Jing Guo 1,  Yanmei Yang 2,  Peixian Li 1,  Ziyan Wang 1,  Sijia Liu 1,  Lulu Zhang 1,  Xiaoyu Zeng 1,  Jincheng Zhai 1,  Xinyong Wang 1,  Qi Zhao 3,  Zhenzhen Chen 1,  Pingping Zhu 1,  Qiankun He 1
Affiliations

Affiliations

  • 1 School of Life Sciences, Zhengzhou University, 100 Kexue Road, Zhengzhou 450001, China.
  • 2 Research Center of Basic Medicine, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 3 Department of oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
PMID: 38665208 DOI: 10.1016/j.isci.2024.109676
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.

Keywords

Cancer; Molecular biology.

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