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- W4286203419 abstract "Abstract Background: Cutaneous squamous cell carcinoma (cSCC) is a malignant proliferation of cutaneous epithelium. Ferroptosis is a new type of cell death involved in cancer progression. M2 macrophage derived exosomes promote cancer proliferation and progression. We intended to investigate the role of M2 macrophages derived exosomes on ferroptosis in cSCC and explore the underlying mechanism. Methods: cSCC samples and adjacent normal tissues were obtained from cSCC patients. Exosomes were isolated from M2 macrophages differentiated from human mononuclear macrophage (THP-1) cells by flow cytometry. Cell viability, iron level, Malondialdehyde (MDA), Lipid ROS, mitochondrial superoxide, mitochondrial membrane potential (MMP) were detected for the validation of ferroptosis. RNAs and proteins were measured using RT-qPCR and western blot. Binding relationships between miR-451a and circ_TNFRSF21 or SLC7A11 were revealed by dual luciferase assay. Results: M2 macrophages were increased in cSCC tissues. M2 macrophages inhibited erastin-induced ferroptosis, which was reversed by exosome inhibitor GW4869. SLC7A11 was up-regulated in cSCC tissues. Erastin treatment reduced cell viability, increased the level of iron and Fe 2+ , upregulated MDA, lipid-ROS, mitochondrial superoxide, and declined MMP, which were reversed by M2 exosomes. Interestingly, circ_TNFRSF21 knockdown antagonized these effects of M2 exosomes. Circ_TNFRSF21 targeted miR-451a to regulate SLC7A11. Erastin-induced ferroptosis was promoted by miR-451a mimics, which was reversed after SLC7A11 overexpression. M2 exosomes inhibited erastin-induced ferroptosis in cSCC cells, which was antagonized by SLC7A11 downregulation or miR-451a upregulation. Conclusion: M2 macrophage exosomes inhibited ferroptosis in cSCC through circ_TNFRSF21/miR-451a/SLC7A11 axis. It is contributed to cSCC progression and may providing a novel target for therapy." @default.
- W4286203419 created "2022-07-21" @default.
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- W4286203419 date "2022-07-21" @default.
- W4286203419 modified "2023-09-27" @default.
- W4286203419 title "M2 macrophage-derived exosomes inhibit ferroptosis via regulating circ_TNFRSF21/ miR-451a/SLC7A11 axis in cutaneous squamous cell carcinoma" @default.
- W4286203419 doi "https://doi.org/10.21203/rs.3.rs-1856562/v1" @default.
- W4286203419 hasPublicationYear "2022" @default.
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