Objective  To investigate the impact of Aurora kinase A (AURKA) on Temozolomide (TMZ) resistance in glioma cells and its regulatory role in ferroptosis.

Methods  The expression profile of AURKA in glioma and its correlation with prognosis were explored using the GEPIA2 database. U87MG/TMZ and LN229/TMZ drug-resistant cell lines were established, and the mRNA and protein expression levels of AURKA were detected by qRT-PCR and Western blot, respectively. AURKA was silenced using siRNA, and dynamic monitoring of lipid peroxidation levels, intracellular iron content, and glutathione peroxidase 4 (GPX4) expression was conducted using BODIPY-C11 staining, FerroOrange iron probe, and immunofluorescence, respectively. Cell viability and IC50 were assessed by the CCK-8 assay, and cell apoptosis was detected by TUNEL staining. Following STAT3 activator treatment, JAK2/STAT3 pathway activity was detected by Western blot, and the molecular association between AURKA and ferroptosis regulation was evaluated.

Results  AURKA was highly expressed in glioma tissues, which was significantly associated with poor prognosis of patients. AURKA expression was significantly upregulated in U87MG/TMZ and LN229/TMZ resistant cells compared to parental cells. After AURKA silencing, lipid peroxidation products and free iron levels increased, while GPX4 protein expression decreased in U87MG/TMZ and LN229/TMZ cells. Ferroptosis inhibitor partially reversed the decrease in cell viability and TMZ resistance induced by AURKA knockdown. AURKA silencing significantly inhibited JAK2/STAT3 pathway activation; exogenous activation of STAT3 (Colivelin) partially restored cell viability and attenuated the promotion of ferroptosis by AURKA knockdown.

Conclusion  AURKA enhances TMZ resistance in glioma cells by inhibiting ferroptosis through the activation of the JAK2/STAT3 pathway.

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