Mechanism of KIAA1199 promoting osteosarcoma cell proliferation by regulating ferroptosis
10.3969/j.issn.1009-0754.2025.04.016
- VernacularTitle:KIAA1199调控铁死亡促进骨肉瘤细胞增殖的机制探究
- Author:
Huisong GONG
1
;
Jun CHENG
;
Youwen DENG
Author Information
1. 528200 广东佛山,广东省中西医结合医院脊柱骨科
- Keywords:
Cell migration-induced protein;
Osteosarcoma;
Cell proliferation;
Ferroptosis
- From:
Journal of Navy Medicine
2025;46(4):392-400
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of cell migration-induced protein(KIAA1199)on the proliferation of osteosarcoma cells.Methods The KIAA1199 gene was knocked down or overexpressed in osteosarcoma cell lines(HOS and U2OS)with high KIAA1199 expression.The expression of KIAA1199 was confirmed by RT-PCR and Western blotting.CCK-8 and colony formation assays were used to determine the effect of KIAA1199 on cell proliferation.CCK-8 and cell viability assays were used to confirm that KIAA1199 promoted osteosarcoma cell proliferation by inhibiting ferroptosis.The BODIPY 581/591 probe was used to investigate the effect of KIAA1199 on cell lipid peroxidation.The effect of KIAA1199 on PTGS2 was investigated by RT-PCR,and the level of ferroptosis related proteins(GPX4,SLC7A11,DHODH,and FSP1)were determined by Western blotting.Results KIAA1199 knockdown inhibited osteosarcoma cell proliferation,which mainly worked by promoting ferroptosis in osteosarcoma cells.Ferrostatin-1(Fer-1,a ferroptosis inhibitor)could reverse the proliferation inhibition caused by KIAA1199 knockdown.Osteosarcoma cells with KIAA1199 knockdown were more sensitive to ferroptosis inducer Erastin,and their lipid peroxidation and PTGS2 mRNA increased significantly.KIAA1199 knockdown resulted in lower expression of GPX4 and SLC7A11 proteins and a lower GSH/GSSG ratio.On the other hand,KIAA1199 overexpression promoted osteosarcoma cell proliferation,made cells more tolerant to Erastin,significantly reduced lipid peroxidation and PTGS2 mRNA levels,and obviously increased the protein expression levels of GPX4 and SLC7A11.Conclusion KIAA1199 inhibits ferroptosis through SLC7A11/GSH/GPX4 pathway,thereby promoting osteosarcoma cell proliferation.
