MicroRNA-199a-5p Inhibits Tumor Proliferation in Melanoma by Mediating HIF-1α.

The expression of hypoxia-inducible factor 1 (HIF-1) is often abundant in human cancer and it is associated with poor prognosis. The present study aimed to investigate its regulation by microRNA (miRNA). The expression of miRNA-199a-5p (miR-199a-5p) in melanoma was detected by quantitative polymerase chain reaction on samples from 25 melanoma patients. The target of miR-199a-5p was predicted and demonstrated by a dual-luciferase reporter system. The effects of miR-199a-5p on melanoma cells were assayed in B16 and HME1 melanoma cell lines. Furthermore, the potential of miR-199a-5p as a therapeutic target was illustrated in xenograft nude mice models. Low expression of miR-199a-5p in tumor melanoma tissue samples from patients was associated with high histological grade and advanced tumor stage. The 3-untranslated region of HIF-1 was identified as a target of miR-199a-5p by Targetscan software. The dual-luciferase reporter assay demonstrated that miR-199a-5p transfection of mimics decreased the luciferase activity significantly (P<0.05). In the B16 and HME1 cell lines, overexpression of miR-199a-5p suppressed cell proliferation and arrested the cell cycle in the G(1) phase. In vivo overexpression of miR-199a-5p significantly suppressed xenograft growth and downregulated the expression of HIF-1 (P<0.05). The results from the present study suggest that miR-199a-5p suppressed melanoma proliferation via HIF-1, suggesting it may be a potential therapeutic target for melanoma treatment.