Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling

• Published in: Biochemistry and biophysics reports 2024-12, Vol.40, p.101864, Article 101864
• Main Authors: Wang, Dingding, Zhang, Xinhao, Guo, Jianxun, Liu, Weijia, Zhou, Yanchi, Wang, Renxian
• Format: Article
• Language: English
• Subjects: EXOSC10; Kinome-wide CRISPR screen; TGF-β signaling
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2024.101864

The TGF-β signaling pathway is closely associated with human health and disease, and the systematic identification of factors involved in the TGF-β signaling pathway significantly contributes to the understanding and treatment of various diseases. Through kinome-wide CRISPR screen, we identified 13 candidate regulatory targets. Notably, the well-known hallmark genes TGFBR1 and TGFBR2 emerged as the top two candidate targets. OXSR1 and EXOSC10 were ranked third and fourth as positive candidate targets, respectively, with EXOSC10 being a novel discovery. Importantly, our findings revealed the down-regulation of OXSR1 and EXOSC10 using CRISPR knockout and RNAi technology effectively suppressed the TGF-β signaling pathway in HeLa and HaCaT cells, providing new insights of TGF-β signaling. •Kinome-wide CRISPR knockout screen systematically identified genes involved in the TGF-β signaling pathway.•A total of 13 candidate targets were identified, with hallmark genes TGFBR1 and TGFBR2 ranking as the top two.•Down-regulation of OXSR1 and EXOSC10 effectively suppressed the TGF-β signaling pathway.