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

Background: Circular 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.

Methods: The 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.

Results: Circ_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.

Conclusion: Circ_0002360 targeted miR-6751-3p to regulate ZNF300 level, thus elevating DDP resistance and promoting the malignant progression of lung cancer cells.