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

J Cell Physiol. 2023 Nov;238(11):2612-2624. doi: 10.1002/jcp.31116. Epub 2023 Sep 3.

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.

Keywords: Oral and Maxillofacial Reconstruction; autophagy; circAP1M2; cisplatin resistance; miR-1249-3p; oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Autophagy-Related Proteins* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin* / pharmacology
  • Cisplatin* / therapeutic use
  • Drug Resistance, Neoplasm* / genetics
  • Humans
  • MicroRNAs* / metabolism
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / drug therapy
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / metabolism

Substances

  • Cisplatin
  • MicroRNAs
  • RNA, Circular
  • ATG9A protein, human
  • Autophagy-Related Proteins
  • MIRN1249 microRNA, human