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

PURPOSE: circRNA plays a key regulatory role in various human tumors. This study was carried out to investigate the molecular mechanism of circBIRC6 in regulating cisplatin (DDP) resistance in choroidal melanoma. METHODS: The expression of circBIRC6 in choroidal melanoma tissues and cells (MUM-2B, MUM-2B/DDP) were detected by RT-qPCR. The roles of circBIRC6 in DDP resistance in choroidal melanoma were analyzed by loss-of-function and overexpression experiments. The DDP inhibition rate was detected by MTT assay. Western blotting was used to analyze the protein levels of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and ERK1/2 (ERK1/MAPK3 and ERK2/MAPK1). The relationship between circBIRC6, miR-503-3p and ERK1/2 was analyzed by CircRIP and dual-luciferase reporter assays. RESULTS: circBIRC6 was significantly upregulated in choroidal melanoma tissues and DDP-resistant MUM-2B cells. CircBIRC6 regulated DDP resistance in choroidal melanoma cells by binding to miR-503-3p. ERK1/2 was directly targeted by miR-503-3p, and ERK1/2 inhibited miR-503-3p-induced DDP resistance. Finally, the expression of circBIRC6 was positively correlated with ERK1/2, and it was verified that circBIRC6 regulated ERK1/2 by targeting miR-503-3p. CONCLUSIONS: CircBIRC6 regulated the expression of ERK1/2 in choroidal melanoma cells and DDP resistance via miR-503-3p. These results suggested that knockdown of circBIRC6 may provide an effective treatment strategy for DDP-resistant choroidal melanoma.