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

Abstract

AbstractCisplatin (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.