| RRC ID |
70862
|
| 著者 |
Supradit K, Boonsri B, Duangdara J, Thitiphatphuvanon T, Suriyonplengsaeng C, Kangsamaksin T, Janvilisri T, Tohtong R, Yacqub-Usman K, Grabowska AM, Bates DO, Wongprasert K.
|
| タイトル |
Inhibition of serine/arginine-rich protein kinase-1 (SRPK1) prevents cholangiocarcinoma cells induced angiogenesis.
|
| ジャーナル |
Toxicol In Vitro
|
| 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.
|
| 巻・号 |
82
|
| ページ |
105385
|
| 公開日 |
2022-8-1
|
| DOI |
10.1016/j.tiv.2022.105385
|
| PII |
S0887-2333(22)00082-0
|
| PMID |
35568131
|
| MeSH |
Arginine
Cholangiocarcinoma*
Humans
Neovascularization, Pathologic / drug therapy
Neovascularization, Pathologic / prevention & control
Protein Isoforms / metabolism
Protein Isoforms / therapeutic use
Protein Serine-Threonine Kinases*
RNA, Messenger
Serine
Serine-Arginine Splicing Factors / genetics
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
|
| IF |
2.959
|
| リソース情報 |
| ヒト・動物細胞 |
RBE(RCB1292)
TFK-1(RCB2537) |
