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.