CircKRT75 augments the cisplatin chemoresistance of nasopharyngeal carcinoma via targeting miR-659/CCAR2 axis.

Cisplatin resistance is a clinical challenge limiting the treatment of nasopharyngeal carcinoma (NPC). CircRNAs have been evidenced as key molecules involved in tumor advancement and drug resistance. The present study aimed to elucidate the potential biological value of circKRT75 in NPC cisplatin resistance. CircKRT75 levels in NPC clinical samples and parental/resistant cell lines were analyzed based on qRT-PCR. CCK-8 and flow cytometry were adopted to assess the impacts of circKRT75 on the growth viability and apoptotic ability of NPC resistant cells. Meanwhile, western blot was performed to detect changes in the expression of apoptosis-related proteins. Bioinformatics analysis predicted miRNAs and mRNAs downstream of circKRT75, and the interaction between circKRT75 and downstream targets was validated by RNA pull-down, dual-luciferase reporter and rescue experiments. CircKRT75 was notably enhanced in NPC tissues and NPC cisplatin-resistant cells. Functional experiments disclosed that circKRT75 silencing repressed NPC-resistant cell growth and promoted apoptosis. Bioinformatics screening identified that circKRT75 performed as a molecular sponge for miR-659, and CCAR2 was a direct target of miR-659. Further rescue assays confirmed that miR-659 inhibitor restored the inhibitory effect of circKRT75 knockdown on the growth of drug-resistant cells, while CCAR2 silencing could reverse the promotion of NPC cisplatin resistance by circKRT75 upregulation. Additionally, animal experiments revealed that circKRT75 knockdown restrained NPC cisplatin resistance in vivo. CircKRT75 contributed to cisplatin resistance in NPC through miR-659/CCAR2 signaling, which provided a novel perspective and direction to solve the problem of chemoresistance in NPC.