Myxoid liposarcoma is a malignant lipogenic tumor that develops in deep soft tissues. While local control rates are good, current chemotherapy options remain ineffective against metastatic disease. Myxoid liposarcoma is characterized by the FUS-DDIT3 fusion oncoprotein that is proposed to function as an aberrant transcription factor, but its exact mechanism of action has remained unclear. To identify the key functional interacting partners of FUS-DDIT3, this study utilized immunoprecipitation-mass spectrometry (IP-MS) to identify the FUS-DDIT3 interactome in whole cell lysates of myxoid liposarcoma cells, and results showed an enrichment of RNA processing proteins. Further quantitative MS analyses of FUS-DDIT3 complexes isolated from nuclear lysates showed that members of several chromatin regulatory complexes were present in the FUS-DDIT3 interactome, including NuRD, SWI/SNF, PRC1, PRC2, and MLL1 COMPASS-like complexes. Co-immunoprecipitation validated the associations of FUS-DDIT3 with BRG1/SMARCA4, BAF155/SMARCC1, BAF57/SMARCE1, and KDM1A. Data from this study provides candidates for functional validation as potential therapeutic targets, particularly for emerging epigenetic drugs.

中文翻译：

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FUS-DDIT3相互作用组在类胶质脂肪肉瘤中。

粘液性脂肪肉瘤是一种在深部软组织中发展的恶性脂肪瘤。尽管局部控制率良好，但目前的化疗方案仍无法有效抵抗转移性疾病。粘液样脂肪肉瘤的特征是FUS-DDIT3融合癌蛋白，被提议作为异常转录因子发挥作用，但其确切的作用机制仍不清楚。为了鉴定FUS-DDIT3的关键功能相互作用伙伴，本研究利用免疫沉淀质谱（IP-MS）鉴定了类脂质脂瘤细胞全细胞裂解液中的FUS-DDIT3相互作用组，结果显示RNA加工蛋白富集。从核裂解物中分离的FUS-DDIT3复合物的进一步定量MS分析表明，FUS-DDIT3相互作用组中存在几种染色质调节复合物的成员，包括NuRD，SWI / SNF，PRC1，PRC2和MLL1 COMPASS类复合物。免疫共沉淀验证了FUS-DDIT3与BRG1 / SMARCA4，BAF155 / SMARCC1，BAF57 / SMARCE1和KDM1A的关联。这项研究的数据为功能验证提供了潜在的治疗靶点，尤其是新兴的表观遗传药物。