Downregulation of MCF2L Promoted the Ferroptosis of Hepatocellular Carcinoma Cells through PI3K/mTOR Pathway in a RhoA/Rac1 Dependent Manner.
Dis Markers
; 2022: 6138941, 2022.
Article
em En
| MEDLINE
| ID: mdl-36330204
ABSTRACT
Methods and Results:
The levels of MCF2L were detected by PCR and western blotting assay. The effect of MCF2L on ferroptosis was confirmed by MTT, colony formation assay, Brdu, in vivo animal experiment, and the content of Iron, GSH, ROS, and MDA. The underlying mechanisms were explored by PCR, western blotting, and affinity precipitation assay. Our findings demonstrated that MCF2L is remarkedly upregulated in HCC tissues, and sorafenib can induce the levels of MCF2L, suggesting that MCF2L might function in sorafenib resistance of HCC. Further analysis showed that downregulation of MCF2L enhances HCC cell death induced by sorafenib, and ferroptosis inhibitor can reverse this process. Subsequent experiments showed that downregulation of MCF2L elevates the content of Iron, ROS, and MDA, which are all indicators of ferroptosis. Finally, mechanism analysis showed that MCF2L regulates the PI3K/AKT pathway in a RhoA/Rac1 dependent manner.Conclusions:
Our study showed that targeting MCF2L may be a hopeful method to overcome sorafenib-resistance through inducing ferroptosis in HCC.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Ferroptose
/
Neoplasias Hepáticas
Limite:
Animals
Idioma:
En
Revista:
Dis Markers
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China