Rsf‑1 regulates malignant melanoma cell viability and chemoresistance via NF‑κB/Bcl‑2 signaling.

Abstract

Remodeling and spacing factor 1 (Rsf-1) 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 Rsf-1 was investigated in 50 cases of malignant melanoma samples using immunohistochemistry. The results revealed that Rsf-1 expression was elevated in 38% of specimens. MTT, colony formation, Transwell and flow cytometry assays were performed to investigate the functions of Rsf-1. Knockdown of Rsf-1 in the MV3 and A375 melanoma cell lines decreased the viability, invasion and cell cycle transition of cells. Conversely, overexpression of Rsf-1 in M14 cells with low endogenous Rsf-1 expression induced opposing effects. Further analysis revealed that Rsf-1 knockdown decreased matrix metalloproteinase-2, cyclin E and phosphorylated-IκB expression. Additionally, Rsf-1 depletion reduced cisplatin resistance and significantly increased the cisplatin-associated apoptotic rate, whereas Rsf-1 overexpression exhibited opposing effects. Rsf-1 also maintained the mitochondrial membrane potential following cisplatin treatment. Analysis of apoptosis-associated proteins revealed that Rsf-1 positively regulated B-cell lymphoma 2 (Bcl-2), cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2, and downregulated Bcl-2-associated X protein expression. Nuclear factor κ-light-chain-enhancer of activated B-cells (NF-κB) inhibition reversed the effects of Rsf-1 on Bcl-2. In conclusion, Rsf-1 was overexpressed in malignant melanoma and may contribute to the malignant behaviors of melanoma cells, possibly via the regulation of NF-κB signaling. Therefore, Rsf-1 may be a potential therapeutic target in the treatment of malignant melanoma.