Rsf­1 regulates malignant melanoma cell viability and chemoresistance via NF­κB/Bcl­2 signaling.

ABSTRACT

Remodeling and spacing factor 1 (Rsf­1) has been reported as overexpressed in numerous cancers; however, its expression, biological functions and mechanisms in malignant melanoma remain unknown. In the present study, the expression of Rsf­1 was investigated in 50 cases of malignant melanoma samples using immunohistochemistry. The results revealed that Rsf­1 expression was elevated in 38% of specimens. MTT, colony formation, Transwell and flow cytometry assays were performed to investigate the functions of Rsf­1. Knockdown of Rsf­1 in the MV3 and A375 melanoma cell lines decreased the viability, invasion and cell cycle transition of cells. Conversely, overexpression of Rsf­1 in M14 cells with low endogenous Rsf­1 expression induced opposing effects. Further analysis revealed that Rsf­1 knockdown decreased matrix metalloproteinase­2, cyclin E and phosphorylated­IκB expression. Additionally, Rsf­1 depletion reduced cisplatin resistance and significantly increased the cisplatin­associated apoptotic rate, whereas Rsf­1 overexpression exhibited opposing effects. Rsf­1 also maintained the mitochondrial membrane potential following cisplatin treatment. Analysis of apoptosis­associated proteins revealed that Rsf­1 positively regulated B­cell lymphoma 2 (Bcl­2), cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2, and downregulated Bcl­2­associated X protein expression. Nuclear factor κ­light­chain­enhancer of activated B­cells (NF­κB) inhibition reversed the effects of Rsf­1 on Bcl­2. In conclusion, Rsf­1 was overexpressed in malignant melanoma and may contribute to the malignant behaviors of melanoma cells, possibly via the regulation of NF­κB signaling. Therefore, Rsf­1 may be a potential therapeutic target in the treatment of malignant melanoma.