Myxofibrosarcoma is genetically complex and lacks effective nonsurgical treatment strategies; thus, elucidation of novel molecular drivers is urgently needed. Reanalyzing public myxofibrosarcoma datasets, we identified mRNA upregulation and recurrent gain of RSF1 and characterized this chromatin remodeling gene. Myxofibrosarcoma cell lines were employed to elucidate the oncogenic mechanisms of RSF1 by genetic manipulation and two IL-1β-neutralizing antibodies (RD24, P2D7KK), highlighting the regulatory basis and targetability of downstream IL-1β-mediated angiogenesis. Tumor samples were assessed for RSF1, IL-1β, and microvascular density (MVD) by immunohistochemistry and for RSF1 gene status by FISH. In vivo, RSF1-silenced and P2D7KK-treated xenografts were analyzed for tumor-promoting effects and the IL-1β-linked therapeutic relevance of RSF1, respectively. In vitro, RSF1 overexpression promoted invasive and angiogenic phenotypes with a stronger proangiogenic effect. RT-PCR profiling identified IL1B as a top-ranking candidate upregulated by RSF1. RSF1 required hSNF2H and CEBP/β to cotransactivate the IL1B promoter, which increased the IL1B mRNA level, IL-1β secretion and angiogenic capacity. Angiogenesis induced by RSF1-upregulated IL-1β was counteracted by IL1B knockdown and both IL-1β-neutralizing antibodies. Clinically, RSF1 overexpression was highly associated with RSF1 amplification, IL-1β overexpression, increased MVD and higher grades (all P ≤ 0.01) and independently predicted shorter disease-specific survival (P = 0.019, hazard ratio: 4.556). In vivo, both RSF1 knockdown and anti-IL-1β P2D7KK (200 μg twice weekly) enabled significant growth inhibition and devascularization in xenografts. In conclusion, RSF1 overexpression, partly attributable to RSF1 amplification, contributes a novel proangiogenic function by partnering with CEBP/β to cotransactivate IL1B, highlighting its prognostic, pathogenetic, and therapeutic relevance in myxofibrosarcomas.

粘液纤维肉瘤基因复杂，缺乏有效的非手术治疗策略；因此，迫切需要阐明新的分子驱动因素。重新分析公共粘液纤维肉瘤数据集，我们确定了RSF1的 mRNA 上调和复发性增益，并表征了这种染色质重塑基因。使用粘液纤维肉瘤细胞系通过基因操作和两种 IL-1β 中和抗体（RD24、P2D7KK）阐明 RSF1 的致癌机制，强调下游 IL-1β 介导的血管生成的调节基础和靶向性。通过免疫组织化学和RSF1评估肿瘤样本的 RSF1、IL-1β 和微血管密度 (MVD)FISH的基因状态。在体内，分别分析了 RSF1 沉默和 P2D7KK 处理的异种移植物的肿瘤促进作用和 RSF1 的 IL-1β 相关治疗相关性。在体外，RSF1 过表达促进了具有更强促血管生成作用的侵袭性和血管生成表型。RT-PCR 分析将IL1B鉴定为由 RSF1 上调的顶级候选物。RSF1 需要 hSNF2H 和 CEBP/β 共同激活IL1B启动子，从而增加IL1B mRNA 水平、IL-1β 分泌和血管生成能力。由 RSF1 上调的 IL-1β 诱导的血管生成被IL1B敲低和两种 IL-1β 中和抗体抵消。临床上，RSF1 过表达与RSF1高度相关扩增、IL-1β 过表达、增加 MVD 和更高等级（所有P  ≤ 0.01）并独立预测更短的疾病特异性生存期（P  = 0.019，风险比：4.556）。在体内，RSF1 敲低和抗 IL-1β P2D7KK（200 μg 每周两次）均能显着抑制异种移植物的生长和去血管化。总之，RSF1 过表达，部分归因于RSF1扩增，通过与 CEBP/β 合作共反式激活IL1B来促进新的促血管生成功能，突出其在粘液纤维肉瘤中的预后、致病和治疗相关性。