顺铂（CDDP）是口腔鳞状细胞癌（OSCC）的一线化疗药物。在治疗过程中易产生耐药性是提高OSCC治疗效果的一项重要挑战。自噬是确保癌细胞在化疗压力下存活的重要因素。我们建立了一个顺铂耐药的OSCC细胞系（CAL27/CDDP），并显示circAP1M2是OSCC中显著上调的环状RNA。circAP1M2的敲减有助于逆转顺铂耐药性，而顺铂耐药的OSCC细胞中增强的自噬活性有助于耐药性。在机制上，我们表明circAP1M2通过miR-1249-3p-ATG9A轴诱导与自噬有关的顺铂耐药性。本研究为新鉴定的环状RNA circAP1M2在OSCC中对药物滥用和广泛癌症治疗的特定影响提供了见解，该治疗可从顺铂中获益。© 2023 Wiley Periodicals LLC.

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.© 2023 Wiley Periodicals LLC.