The regulatory role of exosome-derived miR-3173-5p in targeting the ACSL4 ferroptosis pathway to modulate the malignant phenotype of oral squamous cell carcinoma cells
Objective:An investigation was conducted to determine weather exosome miR-3173-5p from cancer-asso-ciated fibroblasts(CAFs)affects the malignant phenotype of oral cancer and its mechanisms.Methods:The initial step in this study involved establishing primary cultures of normal fibroblasts(NFs)and CAFs,followed by isolation,purification,and veri-fication.Subsequently,exosomes were collected and identified using Transmission Electron Microscope(TEM)and nanoparti-cle tracers.The expression of miR-3173-5p and ACSL4 mRNA,a marker associated with ferroptosis,was analyzed using RT-qPCR.Cell activity,proliferation,migration,and invasion were assessed through various assays including CCK-8,EdU incor-poration,clonogenesis,scratch,and Transwell assays.MiR-3173-5p and ACSL4 were detected using the dual luciferase report-er gene system.Detection of exosomal marker proteins(HSP70,CD81,CD9,CD63,TSG101,and Alix)and expression of ACSL4.Experiments on xenograft tumors confirm the promoting role of miR-3173-5p on oral cancer exosomes derived from CAFs.Results:CAFs exosomes derived from patients with oral cancer were significantly overexpressed with miR-3173-5p,re-sulting in cell proliferation,migration,and invasion.Oral cancer cells overexpressing ACSL4 have reduced miR-3173-5p's capacity to promote malignant phenotypes.An in vivo study has shown that the exosome miR-3173-5p promotes tumor growth in oral cancers.Conclusion:By targeting ACSL4,miR-3173-5p from CAFs-derived exosomes promotes the malignant pheno-type of oral cancer cells.