STEAP3 Affects Ovarian Cancer Progression by Regulating Ferroptosis through the p53/SLC7A11 Pathway

IF 4.4 3区医学 Q2 CELL BIOLOGY

Mediators of Inflammation Pub Date : 2024-02-26 DOI:10.1155/2024/4048527

Yi Han, Lei Fu, Yan Kong, Changqing Jiang, Liying Huang, Hualing Zhang

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引用次数: 0

Abstract

Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.

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STEAP3 通过 p53/SLC7A11 通路调控铁突变，从而影响卵巢癌的进展

卵巢癌（OC）是女性常见的恶性肿瘤，总体生存率较低，而铁突变可能是一种潜在的治疗新策略。前列腺六膜上皮抗原3（STEAP3）是一个与铁凋亡密切相关的基因，但STEAP3在OC中的作用尚未得到深入研究。通过生物信息分析，我们首次发现 STEAP3 在 OC 中高表达，与患者的不良预后显著相关，是一个独立的预后因素。随后，我们通过克隆、划痕和跨孔实验发现，敲除 STEAP3 能显著降低 OC 细胞的增殖和迁移能力。此外，通过检测铁变态反应指标，我们发现敲除 STEAP3 会诱导 OC 细胞铁变态反应。从机理上讲，我们还发现敲除 STEAP3 可通过 p53/SLC7A11 信号通路诱导铁变态反应。通过裸鼠致瘤实验，我们最终验证了敲除 STEAP3 可通过 p53 通路促进铁变态反应，从而抑制肿瘤在体内的生长。总之，我们的研究发现了一种新的治疗靶点，可用于治疗 OC 中的铁凋亡，并探索了其具体的作用机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mediators of Inflammation 医学-免疫学

CiteScore

8.70

自引率

0.00%

发文量

202

审稿时长

4 months

期刊介绍： Mediators of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules.