miR-221-3p通过NRF2/GPX4轴调节铁死亡促进乳腺癌细胞转移的分子机制研究

doi:10.3969/j.issn.1006-6233.2025.01.004

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Abstract Objective: To explore the effect and mechanism of microRNA (miR) -221-3p in regulating ferroptosis to promote breast cancer metastasis. Methods: Human breast cancer cell line MCF-7 was cultured and transfected into MCF-7 cells using miR-221-3p mimic and mimic negative control (NC), real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of miR-221-3p in transfected cells, the kit was used to determine the levels of bivalent iron ion (Fe²⁺), reactive oxygen species (ROS) and reduced glutathione (GSH) in transfected cells. MCF-7 cells were divided into control group, mimic NC group (transfected mimic NC), miR-221-3p mimic group (transfected miR-221-3p mimic), miR-221-3p mimic+Erastin group (transfected miR-221-3p mimic and treated with 10 μmoL/L Erastin). The proliferation activity and the number of migration and invasion of MCF-7 cells were respectively detected by cell counting kit-8 (CCK-8) assay and Transwell assay. Double-labeled immunofluorescence staining was applied to evaluate the expression of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4) in MCF-7 cells. Western blot was used to detect the protein expressions of NRF2, GPX4, solute carrier family 7 member 11 (SLC7A11) and ferritin light chain (FTL) in MCF-7 cells. Results: Compared with cells transfected with blank and mimic NC, cells transfected with miR-221-3p mimic had significantly up-regulated the proliferation activity of MCF-7 cells (P<0.05), elevated the numbers of migration and invasion of MCF-7 cells (P<0.05), decreased Fe²⁺ content (P<0.05), lower ROS level (P<0.05), increased GSH level (P<0.05), enhanced the fluorescence intensity of NRF2 and GPX4 (P<0.05), and up-regulated the proteins expressions of NRF2, GPX4, SLC7A11 and FTL (P<0.05). Compared with cells transfected with miR-221-3p mimic, cells transfected with miR-221-3p mimic+Erastin presented significantly down-regulated proliferation activity of MCF-7 cells, reduced the numbers of migration and invasion of MCF-7 cells (P<0.05), increased Fe²⁺ content (P<0.05), higher ROS level (P<0.05), decreased GSH level (P<0.05), weakened the fluorescence intensity of NRF2 and GPX4 (P<0.05), and down-regulated the proteins expressions of NRF2, GPX4, SLC7A11 and FTL (P<0.05). Conclusion: miR-221-3p can promote breast cancer metastasis by inhibiting ferroptosis, and the mechanism may be related to the activation of NRF2/GPX4 axis.

Key words： Breast cancer MicroRNA-221-3p Ferroptosis Transfer Nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) / glutathione peroxidase 4 (GPX4)

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.01.004 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I1/22

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