School of Queen Mary, Nanchang University and Queen Mary University of London Joint Program, Nanchang 330006, China.
Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Mar 2;53(3):333-341. doi: 10.1093/abbs/gmaa180.
Metformin is a widely prescribed hypoglycemic drug. Many studies have shown its anti-cancer properties. In the present study, we aimed to explore the effect of metformin on breast cancer and clarify the underlying mechanism. Our results showed that metformin induced ferroptosis in MDA-MB-231 cells through upregulating miR-324-3p expression. Overexpression of miR-324-3p inhibited cancer cell viability. miR-324-3p inhibitor promoted cell viability. Further studies showed that the effect of miR-324-3p was mediated by directly targeting glutathione peroxidase 4 (GPX4). miR-324-3p bound to the 3'-UTR of GPX4 and led to the downregulation of GPX4. In vivo studies showed that metformin induced ferroptosis by upregulating miR-324-3p in the xenograft model of breast cancer in mice. Our study suggested that metformin promotes ferroptosis of breast cancer by targeting the miR-324-3p/GPX4 axis. Metformin could act as a potential anti-cancer agent through the induction of ferroptosis.
二甲双胍是一种广泛应用的降血糖药物。许多研究表明其具有抗癌特性。在本研究中，我们旨在探讨二甲双胍对乳腺癌的影响，并阐明其潜在机制。我们的结果表明，二甲双胍通过上调 miR-324-3p 的表达诱导 MDA-MB-231 细胞发生铁死亡。miR-324-3p 的过表达抑制了癌细胞的活力。miR-324-3p 抑制剂促进了细胞活力。进一步的研究表明，miR-324-3p 的作用是通过直接靶向谷胱甘肽过氧化物酶 4（GPX4）介导的。miR-324-3p 结合到 GPX4 的 3'-UTR 上，导致 GPX4 的下调。体内研究表明，二甲双胍通过在小鼠乳腺癌异种移植模型中上调 miR-324-3p 诱导铁死亡。我们的研究表明，二甲双胍通过靶向 miR-324-3p/GPX4 轴促进乳腺癌的铁死亡。二甲双胍可以通过诱导铁死亡作为一种潜在的抗癌药物。
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