FOXQ1通过circ_0000643/miR153/SLC7A11轴抑制乳腺癌的铁死亡和进展。
FOXQ1 inhibits breast cancer ferroptosis and progression via the circ_0000643/miR153/SLC7A11 axis.
发表日期:2023 Aug 15
作者:
Xiaojia Huang, Jinna Wu, Yizhuo Wang, Zhuoyu Xian, Jia Li, Ni Qiu, Hongsheng Li
来源:
Cellular & Molecular Immunology
摘要:
铁死亡调控的失调与乳腺癌进展和治疗反应密切相关。诱导铁死亡可能成为乳腺癌治疗的潜在策略。Forkhead box Q1 (FOXQ1)是一个高表达的致癌转录因子,并与多种肿瘤的不良预后相关。然而,FOXQ1在乳腺癌铁死亡中的具体作用尚不明确。本研究旨在探索FOXQ1在乳腺癌铁死亡中的功能和潜在机制。通过CCK-8、克隆形成、愈合伤口、转染和铁死亡相关实验,我们探究了FOXQ1在乳腺癌铁死亡和进展中的功能。通过公共数据库的生物信息学分析、荧光素酶报告基因实验、RNA免疫共沉淀和染色质免疫沉淀实验,我们研究了FOXQ1在乳腺癌铁死亡和进展中的潜在机制。我们发现FOXQ1在乳腺癌中过度表达,并与较差的生存相关。此外,FOXQ1的抑制抑制了乳腺癌铁死亡和进展。在机械方面,我们证实FOXQ1能够结合circ_0000643宿主基因的启动子,增加circ_0000643的水平,它可以吸附miR153并增强SLC7A11的表达,从而降低乳腺癌细胞的铁死亡。针对FOXQ1/circ_0000643/miR153/SLC7A11轴向可能是乳腺癌治疗的有前景的策略。版权所有 © 2023. Elsevier Inc. 发布。
Dysregulation of ferroptosis is involved in breast cancer progression and therapeutic responses. Inducing ferroptosis can be a potential therapeutic strategy for breast cancer treatment. Forkhead box Q1 (FOXQ1) is an oncogenic transcription factor that highly expressed and related with poor outcomes in various tumors. However, the specific effects of FOXQ1 on ferroptosis in breast cancer is unclear. In this study, we intended to explore the functions and potential mechanisms of FOXQ1 in breast cancer ferroptosis. By CCK-8, colony formation, wound healing, transwell and ferroptosis related assays, we explored the functions of FOXQ1 in breast cancer ferroptosis and progression. Through bioinformatics analysis of public database, luciferase reporter assay, RIP and ChIP assay, we investigated the potential mechanisms of FOXQ1 in breast cancer ferroptosis and progression. We found that FOXQ1 was overexpressed in breast cancer and associated with worse survival. Additionally, inhibition of FOXQ1 suppressed breast cancer ferroptosis and progression. Mechanically, we confirmed that FOXQ1 could bind to the promoter of circ_0000643 host gene to increase the levels of circ_0000643, which could sponge miR153 and enhance the expression of SLC7A11, leading to reduced cell ferroptosis in breast cancer cells. Targeting the FOXQ1/circ_0000643/miR153/SLC7A11 axis could be a promising strategy in breast cancer treatment.Copyright © 2023. Published by Elsevier Inc.