Abstract
AbstractAs the modulation of serine/arginine-rich splicing factor 3 (SRSF3) may be therapeutically beneficial to colorectal cancer (CRC) treatment, the identification of novel SRSF3 inhibitors is highly anticipated. However, pharmaceutical agents targeting SRSF3 have not yet been discovered. Here, we propose a functional SRSF3 inhibitor for CRC therapy and elucidate its antitumor mechanisms. We found high expression of SRSF3 in 70.6% CRC tissues. Silencing SRSF3 markedly inhibits the proliferation and migration of CRC cells through suppression of its target gene 24-dehydrocholesterol reductase (DHCR24). This is evidenced by the links between SRSF3 and DHCR24 in CRC tissues. The novel SRSF3 inhibitor SFI003 exhibits potent antitumor efficacy in vitro and in vivo, which drives apoptosis of CRC cells via the SRSF3/DHCR24/reactive oxygen species (ROS) axis. Moreover, SFI003 is druggable with suitable pharmacokinetic properties, bioavailability, and tumor distribution. Thus, SRSF3 is a novel potential therapeutic target for CRC. Its inhibitor SFI003 may be developed as an anticancer therapeutic.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference40 articles.
1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.
2. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70:145–64.
3. Sakuma K, Sasaki E, Kimura K, Komori K, Shimizu Y, Yatabe Y, et al. HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition. Gut. 2018;67:1103–11.
4. Grinev VV, Barneh F, Ilyushonak IM, Nakjang S, Smink J, van Oort A, et al. RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia. Nat Commun. 2021;12:520.
5. Francies FZ, Hull R, Khanyile R, Dlamini Z. Breast cancer in low-middle income countries: abnormality in splicing and lack of targeted treatment options. Am J Cancer Res. 2020;10:1568–91.
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献