Hypoxia‐inducible factor‐1α can reverse the Adriamycin resistance of breast cancer adjuvant chemotherapy by upregulating transferrin receptor and activating ferroptosis

作者：Xiaojie Yu, Qingqun Guo, Haojie Zhang, Xiaohong Wang, Yong Han, Zhenlin Yang · 发表于：The FASEB Journal · 年份：2024 · DOI：10.1096/fj.202401119r · 被引用次数：21 · 研究领域：Ferroptosis and cancer prognosis、RNA modifications and cancer、Cancer-related molecular mechanisms research

Abstract Breast cancer is a common malignant tumor in women. Ferroptosis, a programmed cell death pathway, is closely associated with breast cancer and its resistance. The transferrin receptor (TFRC) is a key factor in ferroptosis, playing a crucial role in intracellular iron accumulation and the occurrence of ferroptosis. This study investigates the influence and significance of TFRC and its upstream transcription factor hypoxia‐inducible factor‐1α (HIF1α) on the efficacy of neoadjuvant therapy in breast cancer. The differential gene obtained from clinical samples through genetic sequencing is TFRC. Bioinformatics analysis revealed that TFRC expression in breast cancer was significantly greater in breast cancer tissues than in normal tissues, but significantly downregulated in Adriamycin (ADR)‐resistant tissues. Iron‐responsive element‐binding protein 2 (IREB2) interacts with TFRC and participates in ferroptosis. HIF1α, an upstream transcription factor, positively regulates TFRC. Experimental results indicated higher levels of ferroptosis markers in breast cancer tissue than in normal tissue. In the TAC neoadjuvant regimen‐sensitive group, iron ion (Fe 2+ ) and malondialdehyde (MDA) levels were greater than those in the resistant group (all p < .05). Expression levels of TFRC, IREB2, FTH1, and HIF1α were higher in breast cancer tissue compared to normal tissue. Additionally, the expression of the TFRC protein in the TAC neoadjuvant regimen‐sensitive group was significantl...