Hsa_circ_0074269-mediated Upregulation of TUFT1 Through miR-485-5p Increases Cisplatin Resistance in Cervical Cancer.

Most cervical cancer patients are prone to developing acquired cisplatin (DDP) resistance. Hsa_circ_0074269 (circ_0074269) plays a promoting role in cervical cancer, but whether circ_0074269 mediates cervical cancer resistance to DDP is unclear. Expression of circ_0074269 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC50) value, viability, proliferation, colony formation, migration, and apoptosis of DDP-resistant cervical cancer cells were determined. The molecular mechanisms associated with circ_0074269 were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter and RIP assays. Xenograft assay was conducted to validate the effect of circ_0074269 on DDP resistance in vivo. Exosomes were isolated by ultracentrifugation. Circ_0074269 was overexpressed in DDP-resistant cervical cancer samples and cells. Silencing of circ_0074269 elevated DDP sensitivity, repressed DDP-resistant cervical cancer cell proliferation, and induced DDP-resistant cervical cancer cell apoptosis in vivo and in vitro and curbed DDP-resistant cervical cancer cell migration in vitro. And circ_0074269 could regulate DDP resistance via regulating TUFT1 expression via sponging miR-485-5p. More strikingly, circ_0074269 was also overexpressed in exosomes from DDP-resistant cervical cancer cells, and circ_0074269 could be delivered via exosomes. Circ_0074269 facilitated DDP resistance via elevating TUFT1 expression via sponging miR-485-5p, proving novel evidence to offer circ_0074269 as a target for cervical cancer treatment.