Targeting AURKA by MiR-490-3p Overcomes Paclitaxel Resistance in Oral Squamous Cell Carcinoma via NF-κB/STAT3 Signaling

BACKGROUND: Paclitaxel (PTX) resistance remains a major barrier to effective treatment of oral squamous cell carcinoma (OSCC). Although Aurora kinase A (AURKA) has been implicated in tumor progression, its functional role and regulatory mechanisms in PTX resistance are not fully understood. METHODS: PTX-resistant OSCC cell lines (CAL-27/PTX and SCC-9/PTX) were established from their PTX-naïve counterparts (CAL-27 and SCC-9, respectively) through stepwise exposure to increasing concentrations of PTX. AURKA was silenced using shRNA or regulated by miR-490-3p overexpression. Cell viability, apoptosis, migration, and invasion were assessed in vitro. NF-κB and STAT3 signaling activities were evaluated as downstream effectors. Direct targeting of AURKA by miR-490-3p was validated using dual-luciferase reporter assays. A xenograft model was used to assess the in vivo effects of AURKA knockdown on tumor growth and drug response. RESULTS: AURKA was significantly upregulated in PTX-resistant OSCC cells, accompanied by activation of NF-κB and STAT3 signaling. Functional inhibition of AURKA or restoration of miR-490-3p enhanced PTX sensitivity, promoted apoptosis, and suppressed migratory and invasive behaviors, together with attenuation of NF-κB/STAT3 activity. Mechanistically, miR-490-3p directly bound to the 3'-UTR of AURKA and negatively regulated its expression, whereas AURKA re-expression reversed these effects. In vivo, AURKA knockdown suppressed tumor growth, increased apoptotic activity, and inhibited NF-κB/STAT3 signaling in PTX-resistant xenografts. CONCLUSION: These findings identify a functional miR-490-3p/AURKA axis that regulates PTX resistance in OSCC through coordinated modulation of NF-κB and STAT3 signaling. Targeting this pathway may provide a promising strategy to overcome chemoresistance and inhibit OSCC progression.