EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways

Abstract

Abstract Melanoma is a rare, fatal type of skin tumor. Although EPH receptor A3 (EphA3) is deregulated in melanoma, its detailed role remained uncharacterized. Using real time quantitative PCR analysis and western blotting, EphA3 was identified to be upregulated in melanoma tissues and cells, while miR-3666 showed an opposite expression trend. Cell counting kit-8, scratch wound, and in vivo assays proved that EphA3 silence inhibited the melanoma cell proliferation and migration and retarded tumor growth in vivo. Furthermore, western blotting results displayed that EphA3 silence resulted in a low expression of p38-MAPK and p-ERK1/2. Mechanically, miR-3666 was proved to target EphA3 3′UTR by the luciferase reporter assay. Furthermore, miR-3666 mimic compromised the driven melanoma cell proliferation and migration by EphA3 overexpression. In addition, induction of ERK1/2 and p38 MAPK pathways offset the positive effect of EphA3 overexpression on melanoma cells. In conclusion, miR-3666 downregulated EphA3 expression and retarded melanoma malignancy via inactivating ERK1/2 and p38 MAPK pathways. Hence, miR-3666/EphA3 axis may represent a druggable target against melanoma progression.