The Mechanism of BPTF Mediating SLC40A1 in Regulating Ferroptosis and Promoting Glioma Growth,Invasion and Metastasis
10.3870/j.issn.1672-0741.25.05.017
- VernacularTitle:BPTF介导SLC40A1调节铁死亡促进胶质瘤生长、侵袭和转移的机制研究
- Author:
Zhiren LIN
1
;
Yanling PAN
;
Yanxing ZHU
Author Information
1. 海南省海口市人民医院放射肿瘤治疗科,海口 570208
- Publication Type:Journal Article
- Keywords:
glioma;
BPTF;
SLC40A1;
ferroptosis;
c-Myc
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(4):507-512,534
- CountryChina
- Language:Chinese
-
Abstract:
Objective To verify the mechanism of bromodomain PHD finger transcription factor(BPTF)affecting develop-ment of glioma and ferroptosis by regulating the expression of solute carrier family 40 member 1(SLC40A1)in glioma cells by in v itro and invivo experiments.Methods U87MG cells were divided into sh-NC group,sh-BPTF group,sh-BPTF+ov-NC group and sh-BPTF+ov-SLC40A1 group.Cell lines were stably transfected by lentivirus,and the transfection efficiency was verified by qRT-PCR and Western blotting.Cell proliferation ability was detected by CCK-8 and plate clone formation test.Cell migra-tion and invasion ability were detected by Transwell.Cells were injected subcutaneously into nude mice to detect the tumor growth.To evaluate theferroptosis of cells,the reactive oxygen species(ROS)level,iron content,malondialdehyde(MDA)con-tent and reduced glutathione/oxidized glutathione(GSH/GSSG)ratio in cells were detected by corresponding kits.Co-immuno-precipitation(Co-IP)experiment was used to verify the interaction between BPTF and c-Myc protein.Chromatin immunoprecipi-tation(ChIP)experiment was used to verify that BPTF and c-Myc combined with SLC40A1 promoter.Double luciferase reporter gene experiment was used to verify theeffect of BPTF on SLC40A1 transcription.Results After BPTF knockdown,theexpres-sion of SLC40A1 in glioma cell was decreased,cell proliferation,migration,invasion in vitro,and tumor growth in vivo were in-hibited,iron content,ROS level and MDA content in cells were increased,and GSH/GSSG ratio in cell was de-creased.Overexpression of SLC40A1 reversed the inhibitory effect of BPTF on the proliferation,migration,invasion and tumor grow th in vivo,decreased the iron content,ROS level and MDA content in cells,and increased the GSH/GSSG ratio in cells.There was an interaction between BPTF and c-Myc proteins in gliomacells.A potential binding site of c-Mycin SLC40A1 promoter was verified,BPTF and c-Myc protein bound to SLC40A1 promoter.BPTF knockdown reduced the transcriptional ac-tivity of SLC40A1 promoter,and BPTF knockdown after binding site mutation did not affect the transcriptional activity of SLC40A1 promoter.Conclusion BPTF may upregulate the expression of its downstream target gene SLC40A1 by interacting with c-Myc,thereby inhibiting ferroptosis in glioma cells and promoting glioma progression.
