Circ_0109291 Promotes Cisplatin Resistance of Oral Squamous Cell Carcinoma by Sponging miR-188-3p to Increase ABCB1 Expression.

Abstract

Background: The occurrence of cisplatin (DDP) resistance in oral squamous cell carcinoma (OSCC) is a major challenge for OSCC treatment. Circular RNAs (circRNAs) have been associated with the development of cancer resistance, but the role of circ_0109291 in DDP resistance of OSCC is unclear. Methods: The expression of circ_0109291 and microRNA-188-3p (miR-188-3p) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit 8 (CCK8) assay, colony formation assay, and flow cytometry were performed to measure the DDP resistance, proliferation, and apoptosis of cells. The levels of apoptosis-related proteins and ATP-binding cassette sub-family B member 1 (ABCB1) protein were assessed via Western blot (WB) analysis. In addition, dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assay were used to illuminate the mechanism of circ_0109291. Animal experiments were employed to confirm the effect of circ_0109291 on OSCC tumor growth in vivo. Results: Circ_0109291 was higher expressed in DDP-resistant OSCC tissues and cells, and its knockdown suppressed proliferation and resistance and enhanced the apoptosis of OSCC cells. MiR-188-3p could be sponged by circ_0109291, and its overexpression had an inhibition effect on the DDP resistance of OSCC cells. ABCB1 was a target of miR-188-3p. Further experiments confirmed that both miR-188-3p inhibitor and ABCB1 overexpression also could invert the suppression effect of circ_0109291 silencing on the DDP resistance of OSCC cells. In vivo experiments revealed that silenced circ_0109291 could improve the sensitivity of the tumor to DDP. Conclusion: Circ_0109291 could promote the DDP resistance of OSCC, suggesting that silenced circ_0109291 might be a key step to inhibit OSCC resistance.