1. Academic Validation
  2. A novel SRSF3 inhibitor, SFI003, exerts anticancer activity against colorectal cancer by modulating the SRSF3/DHCR24/ROS axis

A novel SRSF3 inhibitor, SFI003, exerts anticancer activity against colorectal cancer by modulating the SRSF3/DHCR24/ROS axis

  • Cell Death Discov. 2022 May 2;8(1):238. doi: 10.1038/s41420-022-01039-9.
Yawen Zhang 1 Mengmeng Wang 1 Fanyi Meng 1 Man Yang 1 Yinshuang Chen 1 Xuqin Guo 1 Weiwei Wang 1 Yifan Zhu 1 Yundi Guo 2 Chunlai Feng 3 Shen Tian 1 Hongjian Zhang 1 Huanqiu Li 4 Jing Sun 5 Weipeng Wang 6
Affiliations

Affiliations

  • 1 Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
  • 2 Institute of Medical Technology, Suzhou Vocational Health College, Suzhou, 215009, China.
  • 3 School of Pharmacy, Jiangsu University, Zhenjiang, 212013, China.
  • 4 Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. huanqiuli@suda.edu.cn.
  • 5 Institute of Medical Technology, Suzhou Vocational Health College, Suzhou, 215009, China. jsun@szhct.edu.cn.
  • 6 Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. wangweipeng@suda.edu.cn.
Abstract

As 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.

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