EFHD2 regulates the NOX4/ROS pathway to initiate glucose metabolism reprogramming and promote breast cancer progression
10.3969/j.issn.1671-7856.2024.09.008
- VernacularTitle:EFHD2调节NOX4/ROS通路启动糖代谢重编程促进乳腺癌进展的机制研究
- Author:
Mingfei XU
1
;
Yi ZHANG
;
Ruyi KANG
;
Chaoyue LIU
Author Information
1. 川北医学院基础医学与法医学院人体解剖学教研室,四川南充 637000
- Keywords:
breast cancer;
metabolic reprogramming;
NOX4/ROS signaling pathway;
EFHD2;
immune escape
- From:
Chinese Journal of Comparative Medicine
2024;34(9):66-75
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which EFHD2 affects the occurrence and progression of breast cancer based on the NOX4/ROS signaling pathway.Methods Cells were divided into an NC-shRNA group and EFHD2-shRNA group.A lentiviral vector for EFHD2 silencing and a control vector were constructed and used to transfect MDA-MB-23 and MCF-7 breast cancer cells.The transfection efficiency was verified by qRT-PCR.A CCK8 assay was used to detect cell proliferation activity.A plate cloning assay was employed to measure cell colony formation ability.A scratch test was used to detect cell migration,and a Transwell assay used to assess cell invasion.Flow cytometry was applied to detect apoptosis and ROS levels.qRT-PCR was used to analyze the mRNA expression of GLUT1,PDK1,PFK1,PKM2,PDH,and LDH,while Western blot was applied to detect the expression of Cleaved caspase-3,MMP-2,and NOX4 proteins.Results Compared with the NC-shRNA group,the EFHD2-shRNA group's EFHD2 expression was significantly decreased and its cell survival and colony formation ability were weakened.The apoptosis rate and the expression of the pro-apoptotic protein Cleaved caspase-3 increased.The cell migration distance was shortened,while the number of invading cells and the expression of MMP-2,which promotes migration and invasion,were decreased.The levels of lactic acid and GLUT1,PDK1,PFK1,PKM2,and LDH decreased,while the levels of ATP and PDH increased.Streaming result showed that ROS levels were reduced and NOX4 protein was down-regulated after silencing EFHD2.Conclusions EFHD2 inhibits ROS production by regulating the NOX4/ROS signaling pathway,causing lactic acid and glucose accumulation,promoting the apoptosis of breast cancer cells,and inhibiting cell proliferation,migration,and invasion.
