Hsa-miR-26a-5p improves OSCC sensitivity to ferroptosis by inhibiting SLC7A11

Abstract

ObjectiveSLC7A11 plays a crucial role in ferroptosis and is upregulated in oral squamous cell carcinoma (OSCC) samples. This study mainly aimed to elucidate the association of SLC7A11 with ferroptosis in OSCC and analyze its upstream regulatory mechanism. DesignThe expression of SLC7A11 in OSCC and paracancerous tissues was detected. After administration of different concentrations of erastin to OSCC cells, cell viability was examined by MTT, and changes in GSH, MDA and Fe2+ concentrations were determined. Then, mitochondrial changes were examined by transmission electron microscopy. Bioinformatics analysis was performed to predict the upstream regulatory miRNA of SLC7A11, and the interaction between miR-26a and SLC7A11 was confirmed by a dual luciferase reporter gene. The effect of miR-26a mimics on ferroptosis resistance was also examined. ResultsSLC7A11 expression was upregulated in both OSCC patients and cells, with high SLC7A11 expression levels in SCC-9 cells with an IC50 = 69.75 μM for erastin and low SLC7A11 expression levels in SCC-4 cells with an IC50 = 8.463 μM for erastin. SCC-9 exhibited a higher level of ferroptosis resistance than SCC-4. miR-26a-5p expression was downregulated in both OSCC patients and cells. A dual luciferase reporter assay confirmed that miR-26a-5p targets binding to the SLC7A11 3′UTR. Transfection of the miR-26a mimic significantly inhibited the viability of OSCC cells and promoted erastin-induced cellular ferroptosis. Transfection of miR-26a inhibitor gave the opposite result. Overexpression of SLC7A11 significantly reversed miR-26a mimic ferroptosis induction. ConclusionmiR-26a-5p can exert OSCC inhibitory effects by regulating SLC7A11 and promote ferroptosis in OSCC cells by inhibiting SLC7A11.