Rsf?1 regulates malignant melanoma cell viability and chemoresistance via NF??B/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?I?B 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 ??light?chain?enhancer of activated B?cells (NF??B) 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??B signaling. Therefore, Rsf?1 may be a potential therapeutic target in the treatment of malignant melanoma.

SUBMITTER: He J 

PROVIDER: S-EPMC6755232 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature