Circular RNA SET domain protein 3 promotes nasopharyngeal carcinoma proliferation, cisplatin resistance, and protein kinase B / mammalian target of rapamycin pathway activation by modulating microRNA-147a expression

Abstract

ABSTRACT Circular RNA (circRNA) plays a crucial role in the establishment and progression of nasopharyngeal carcinoma (NPC). Understanding the role of circRNA in NPC is helpful to find new therapeutic targets for NPC. The purpose of this study was to explore the effects of circRNA SET domain protein 3 (circSETD3) on protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway and cisplatin (DDP) resistance to NPC and explore its downstream mechanism. The results showed that circSETD3 was upregulated in NPC tissues and was related to DDP resistance to NPC. Functional experiments revealed that circSETD3 knockdown inhibited NPC proliferation and increased DDP sensitivity and apoptosis rate. The promotion effect of circSETD3 overexpression on NPC proliferation and DDP resistance and inhibition effect on apoptosis was reversed by elevated miR-147a. CircSETD3 knockdown or miR-147a overexpression prevented Akt/mTOR pathway’s activation. In terms of the mechanism, circSETD3 acted as a sponge for miR-147a. Xenotransplantation experiments showed that knockdown circSETD3 or DDP treatment could restrain tumor growth, and the effect of DDP was enhanced by knockdown of circSETD3. In conclusion, the results of this study confirm that circSETD3 promotes NPC proliferation and DDP resistance by regulating miR-147a, and circSETD3/miR-147a axis may serve as a potential therapeutic target for NPC in the future.