Chen Sheng, Luo Yangyong, Ruan Simin, Su Guosen, Huang Guoxing
Department of Breast Disease, GaoZhou People'Hospital, Guangdong Province, 89 Xiguan Road, Maoming City, Gaozhou City, 525200, China.
Hereditas. 2025 Jan 27;162(1):10. doi: 10.1186/s41065-025-00372-0.
Ferroptosis has emerged as a promising therapeutic target in cancer treatment. CEP55, a key regulator of cell mitosis, plays a significant role in the tumorigenesis of many malignancies. In this study, we elucidated the function of CEP55 in the ferroptosis of breast cancer (BC).
The protein levels of CEP55 and ILF3 were detected by immunoblotting or immunohistochemistry, and their mRNA levels were assessed by quantitative PCR. Cell invasion and migration were evaluated by transwell assay. Cell apoptosis and colony formation were tested by flow cytometry and colony formation assays, respectively. RNA immunoprecipitation (RIP) experiment and CEP55 mRNA stability assay were used to validate the relationship between ILF3 and CEP55 mRNA. Subcutaneous xenograft studies were performed to analyze the role of ILF3 depletion in tumor growth.
CEP55 and ILF3 were upregulated in most of human BC samples and MDA-MB-231 and MCF-7 BC cells. The depletion of CEP55 or ILF3 impaired the growth, invasion, and migration of MDA-MB-231 and MCF-7 cells, while promoted their ferroptosis and apoptosis. Mechanistically, ILF3 stabilized CEP55 mRNA to regulate CEP55 expression in BC cells. CEP55 restoration partially rescued the malignant potential defects of ILF3-depleted BC cells and attenuates their ferroptosis. Moreover, ILF3 depletion enhanced the anti-tumor growth activity of the ferroptosis inducer erastin in MDA-MB-231 subcutaneous xenograft tumors.
Our observations indicate that the depletion of ILF3 impairs the malignant potential of BC cells and promotes their ferroptosis by downregulating CEP55 expression. Silencing ILF3 or CEP55 could represent a potential therapeutic strategy for BC treatment.
铁死亡已成为癌症治疗中一个有前景的治疗靶点。CEP55是细胞有丝分裂的关键调节因子，在许多恶性肿瘤的发生发展中起重要作用。在本研究中，我们阐明了CEP55在乳腺癌（BC）铁死亡中的作用。
通过免疫印迹或免疫组织化学检测CEP55和ILF3的蛋白水平，通过定量PCR评估它们的mRNA水平。通过Transwell实验评估细胞侵袭和迁移能力。分别通过流式细胞术和集落形成实验检测细胞凋亡和集落形成情况。采用RNA免疫沉淀（RIP）实验和CEP55 mRNA稳定性实验验证ILF3与CEP55 mRNA之间的关系。进行皮下异种移植研究以分析ILF3缺失对肿瘤生长的作用。
CEP55和ILF3在大多数人BC样本以及MDA-MB-231和MCF-7 BC细胞中上调。CEP55或ILF3的缺失损害了MDA-MB-231和MCF-7细胞的生长、侵袭和迁移能力，同时促进了它们的铁死亡和凋亡。机制上，ILF3稳定CEP55 mRNA以调节BC细胞中CEP55的表达。CEP55的恢复部分挽救了ILF3缺失的BC细胞的恶性潜能缺陷并减弱了它们的铁死亡。此外，ILF3缺失增强了铁死亡诱导剂埃拉斯汀在MDA-MB-231皮下异种移植肿瘤中的抗肿瘤生长活性。
我们的观察结果表明，ILF3的缺失损害了BC细胞的恶性潜能，并通过下调CEP55表达促进其铁死亡。沉默ILF3或CEP55可能代表一种潜在的BC治疗策略。
