Cisplatin resistance and malignant behaviors of lung cancer cells are promoted by circ_0002360 via targeting miR-6751-3p to regulate the expression of ZNF300.

Abstract

BackgroundCircular RNAs (circRNAs) are key regulators in oncogenesis and chemoresistance of human cancers. Herein, we focused on the roles of circ_0002360 in regulating lung cancer progression and cisplatin (DDP) resistance.MethodsThe detection of circ_0002360, microRNA‐6751‐3p (miR‐6751‐3p) and zinc finger protein 300 (ZNF300) was conducted via reverse transcription‐quantitative polymerase chain reaction assay. Cell sensitivity was determined using cell counting kit‐8 assay. Proliferation detection was performed by colony formation assay and EdU assay. The migrated cells were examined via transwell assay. Cell apoptosis analysis was carried out through flow cytometry and caspase 3 activity assay. Western blot was used to examine the protein levels. Target interaction was confirmed through dual‐luciferase reporter assay and RNA immunoprecipitation assay. Circ_0002360 function in vivo was performed via xenograft tumor assay.ResultsCirc_0002360 was overexpressed in DDP‐resistant lung cancer tissues and cells. Silencing circ_0002360 inhibited DDP resistance, proliferation and migration but enhanced apoptosis of DDP‐resistant cells. Circ_0002360 could elevate ZNF300 expression. DDP resistance and lung cancer progression were also impeded by ZNF300 downregulation. ZNF300 overexpression reversed the function of circ_0002360 knockdown in DDP‐resistant lung cancer cells. The regulation of circ_0002360 for ZNF300 was achieved by sponging miR‐6751‐3p. Circ_0002360 promoted DDP resistance in xenograft mice through mediating the miR‐6751‐3p/ZNF300 axis.ConclusionCirc_0002360 targeted miR‐6751‐3p to regulate ZNF300 level, thus elevating DDP resistance and promoting the malignant progression of lung cancer cells.