CircUBAP2 inhibits cisplatin resistance in gastric cancer via miR-300/KAT6B axis.

Abstract

Circular RNAs play an important role in regulating cisplatin (CDDP) resistance in gastric cancer (GC). The aim of this study was to examine the role and downstream regulation mechanisms of circUBAP2 in CDDP resistance of GC. The expression of circUBAP2 in GC and its correlation with the prognosis of GC patients were analyzed using qRT-PCR and the Kaplan-Meier plotter database. The effects of circUBAP2 on cell viability and apoptosis were investigated by Cell Counting Kit 8 assay and flow cytometry. The expressions of drug-resistance-related proteins, P-gp and MRP1, were detected by Western blot. The interaction between circUBAP2 and miR-300 was confirmed using RNA pulldown and immunoprecipitation assays. The correlation between miR-300 and KAT6B was assessed using dual-luciferase reporter assay and TCGA database. CircUBAP2 was downregulated in GC tissues and cell lines, and correlated with the poor prognosis of GC. In addition, circUBAP2 enhanced apoptosis but inhibited cell viability and the CDDP resistance of GC cells in vitro . CircUBAP2 acted as a sponge of microRNA-300 (miR-300) and was negatively correlated with miR-300. Moreover, the upregulation of miR-300 partially removed the effects of circUBAP2 on cell viability, apoptosis and CDDP resistance in GC cells. MiR-300 directly targeted to lysine acetyltransferase 6B (KAT6B), and KAT6B overexpression showed an inhibitory effect on cell viability and CDDP resistance of GC cells. Our data suggested that the circUBAP2/miR-300/KAT6B axis was involved in the inhibition of CDDP resistance in GC, which might provide a novel focus for potential GC therapy.