circBIRC6 regulates cisplatin resistance of choroidal melanoma via positively modulating ERK by sponging miR-503-3p

Abstract

Abstract Background/AimscircRNA plays a key regulatory role in various human tumors. This study was carried out to investigate the molecular mechanism of circBIRC6 in the regulation of choroidal melanoma cisplatin (DDP) resistance. MethodsThe expression of circBIRC6 in choroidal melanoma tissues and cells (MUM-2B, MUM-2B / DDP) was detected by RT-qPCR. The function of circBIRC6 in DDP resistance of choroidal melanoma was analyzed by functional loss and overexpression experiments. DDP inhibition rate was detected by MTT method. Western blot was used to analysis the protein levels of P-gp, MRP1 and ERK. The relationship between circBIRC6, miR-503-3p and ERK was analyzed by CircRIP and luciferase reporter vector assay.ResultcircBIRC6 was up-regulated in choroidal melanoma, and it was significantly raised in choroidal melanoma tissues and cells that are resistant to DDP. CircBIRC6 regulated DDP resistance of choroidal melanoma cells by binding to miR-503-3p. ERK was directly targeted by miR-503-3p, and ERK inhibited miR-503-3p-induced DDP resistance. Finally, the expression of circBIRC6 was positively correlated with ERK, and it was verified that circBIRC6 regulated ERK by targeting miR-503-3p.ConclusionCircBIRC6 regulated the expression of ERK choroidal melanoma cells and DDP resistance via miR-503-3p. These results suggested that the knockout of circBIRC6 may provide an effective treatment strategy for choroidal melanoma.