2. Academic Validation
  3. Inhibition of serine/arginine-rich protein kinase-1 (SRPK1) prevents cholangiocarcinoma cells induced angiogenesis

Inhibition of serine/arginine-rich protein kinase-1 (SRPK1) prevents cholangiocarcinoma cells induced angiogenesis

  • Toxicol In Vitro. 2022 Aug;82:105385. doi: 10.1016/j.tiv.2022.105385.
Kittiya Supradit 1,  Boonyakorn Boonsri 2,  Jinchutha Duangdara 1,  Thanvarin Thitiphatphuvanon 3,  Chinnawut Suriyonplengsaeng 1,  Thaned Kangsamaksin 4,  Tavan Janvilisri 4,  Rutaiwan Tohtong 4,  Kiren Yacqub-Usman 5,  Anna M Grabowska 4,  David O Bates 4,  Kanokpan Wongprasert 6
Affiliations

Affiliations

  • 1 Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 2 Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand.
  • 3 Faculty of Medicine Establishment Project , Kasetsart University, Bangkok, Thailand.
  • 4 Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 5 Division of Cancer and Stem Cells, Centre for Cancer Sciences, Biodiscovery Institute, School of Medicine, University of Nottingham, United Kingdom.
  • 6 Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: kanokpan.won@mahidol.ac.th.
PMID: 35568131 DOI: 10.1016/j.tiv.2022.105385
Abstract

The serine/arginine-rich protein kinase-1 (SRPK1) is an Enzyme that has an essential role in regulating numerous aspects of mRNA splicing. SRPK1 has been reported to be overexpressed in multiple cancers, suggesting it as a promising therapeutic target in oncology. No previous studies reported the role of SRPK1 in cholangiocarcinoma (CCA) cells. This study aimed to examine the expression of SRPK1 and the effects of SRPK1 inhibition on the viability and angiogenesis activity of CCA cells using a selective SRPK1 inhibitor, SPHINX31. Here, we demonstrate that SPHINX31 (0.3-10 μM) had no inhibitory effects on CCA cells' viability and proliferation. However, SPHINX31 decreased the mRNA expression of pro-angiogenic VEGF-A165a isoform. In addition, SPHINX31 attenuated SRSF1 phosphorylation and nuclear localization, and increased the ratio of VEGF-A165b/total VEGF-A proteins. Moreover, when HUVECs were grown in conditioned medium from SPHINX31-treated CCA cells, migration slowed, and tube formation decreased. The present study demonstrates that targeting SRPK1 in CCA cells effectively attenuates angiogenesis by suppressing pro-angiogenic VEGF-A isoform splicing. These findings suggest a potential therapeutic treatment using SRPK1 inhibitors for the inhibition of angiogenesis in cholangiocarcinoma.

Keywords

Angiogenesis; Cholangiocarcinoma; Endothelial cells; SPHINX31; SRPK1; VEGF-A.

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