CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression

Abstract

Ovarian cancer is a gynecological tumor with a poor prognosis. The chemotherapy failure and recurrence induced by paclitaxel (Ptx) resistance are the main reason for the failure of ovarian cancer treatment. In this study, we aimed to explore the role of circular RNA (circRNA) in the regulation of Ptx resistance in ovarian cancer. Quantitative reverse transcription PCR was performed to detect the expression of circRNA SET domain bifurcated histone lysine methyltransferase 1 (circSETDB1), microRNA (miR)-508-3p and ATP-binding cassette subfamily C member 1 (ABCC1) mRNA. The effects of circSETDB1 on Ptx resistance were explored by cell counting kit-8, 5-ethynyl-2′-deoxyuridine, and flow cytometry experiments in vitro. The protein level was assessed by western blot. Dual-luciferase reporter and RNA pull-down assays were carried out to confirm the interactions among circSETDB1, miR-508-3p, and ABCC1. Xenograft tumor experiment was performed to investigate the effect of circSETDB1 on Ptx resistance in vivo. CircSETDB1 was highly expressed in Ptx-resistant ovarian cancer. CircSETDB1 knockdown inhibited cell proliferation viability, half maximal inhibitory concentration value of Ptx, cell cycle progression, and induced cell apoptosis in Ptx-resistant ovarian cancer cells. miR-508-3p was a target of circSETDB1, and inhibition of miR-508-3p overturned the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. miR-508-5p could bind to ABCC1. Overexpression of ABCC1 reversed the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. CircSETDB1 knockdown also enhanced Ptx sensitivity in vivo. In conclusion, circSETDB1 regulated Ptx resistance of ovarian cancer by targeting miR-508-3p/ABCC1 axis.