circAP1M2 activates ATG9A-associated autophagy by inhibiting miR-1249-3p to promote cisplatin resistance in oral squamous cell carcinoma.

ABSTRACT

Cisplatin (CDDP) is the first-line chemotherapeutic agent for oral squamous cell carcinoma (OSCC). Susceptibility to drug resistance during treatment is a significant challenge in enhancing the therapeutic efficacy of OSCC. Autophagy is an essential element to guarantee the cancer cells' survival under chemo-stress conditions. We established a cisplatin-resistant OSCC cell line (CAL27/CDDP) and showed that circAP1M2 is a remarkably upregulated circular RNA in OSCC. Knockdown of circAP1M2 contributes to reversing cisplatin chemoresistance in vivo, while enhanced autophagic activity in cisplatin-resistant OSCC cells contributes to chemoresistance. Mechanistically, we showed that circAP1M2 induces autophagy-associated cisplatin resistance via the miR-1249-3p-ATG9A axis in OSCC cells. This study provides insights into the specific influence of a newly identified circular RNA circAP1M2 in OSCC regarding drug abuse and the treatment of a broad range of cancers that can benefit from cisplatin.