Department of Pathology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
Mol Med Rep. 2019 Oct;20(4):3487-3498. doi: 10.3892/mmr.2019.10610. Epub 2019 Aug 23.
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.
重塑和间隔因子 1(Rsf-1)已被报道在许多癌症中过度表达;然而,其在恶性黑色素瘤中的表达、生物学功能和机制尚不清楚。在本研究中,通过免疫组织化学法检测了 50 例恶性黑色素瘤样本中 Rsf-1 的表达。结果显示,38%的标本中 Rsf-1 表达上调。通过 MTT、集落形成、Transwell 和流式细胞术实验研究了 Rsf-1 的功能。在 MV3 和 A375 黑色素瘤细胞系中敲低 Rsf-1 降低了细胞的活力、侵袭和细胞周期转变。相反,在低内源性 Rsf-1 表达的 M14 细胞中过表达 Rsf-1 诱导了相反的效应。进一步分析显示,Rsf-1 敲低降低了基质金属蛋白酶-2、细胞周期蛋白 E 和磷酸化-IκB 的表达。此外,Rsf-1 耗竭降低了顺铂耐药性,并显著增加了顺铂相关的凋亡率,而 Rsf-1 过表达则表现出相反的效果。Rsf-1 还维持了顺铂处理后的线粒体膜电位。凋亡相关蛋白分析显示,Rsf-1 正向调节 B 细胞淋巴瘤 2(Bcl-2)、细胞凋亡抑制蛋白 1(cIAP1)和 cIAP2,下调 Bcl-2 相关 X 蛋白的表达。核因子 κ-轻链增强子的 B 细胞激活(NF-κB)抑制逆转了 Rsf-1 对 Bcl-2 的作用。总之,Rsf-1 在恶性黑色素瘤中过度表达,可能通过调节 NF-κB 信号通路促进黑色素瘤细胞的恶性行为。因此,Rsf-1 可能是治疗恶性黑色素瘤的潜在治疗靶点。