Children's Cancer Institute, Porto Alegre, Brazil.
National Science and Technology Institute for Children's Cancer Biology and Pediatric Oncology - INCT BioOncoPed, Porto Alegre, Brazil.
FEBS Lett. 2023 Oct;597(19):2446-2460. doi: 10.1002/1873-3468.14724. Epub 2023 Aug 28.
Ewing sarcoma (ES) is a highly aggressive pediatric tumor driven by the RNA-binding protein EWS (EWS)/friend leukemia integration 1 transcription factor (FLI1) chimeric transcription factor, which is involved in epithelial-mesenchymal transition (EMT). EMT stabilizes a hybrid cell state, boosting metastatic potential and drug resistance. Nevertheless, the mechanisms underlying the maintenance of this hybrid phenotype in ES remain elusive. Our study proposes a logical EMT model for ES, highlighting zinc finger E-box-binding homeobox 2 (ZEB2), miR-145, and miR-200 circuits that maintain hybrid states. The model aligns with experimental findings and reveals a previously unknown circuit supporting the mesenchymal phenotype. These insights emphasize the role of ZEB2 in the maintenance of the hybrid state in ES.
尤因肉瘤（ES）是一种高度侵袭性的儿科肿瘤，由 RNA 结合蛋白 EWS（EWS）/白血病融合基因 1 转录因子（FLI1）嵌合转录因子驱动，该因子参与上皮-间充质转化（EMT）。EMT 稳定了杂交细胞状态，增强了转移潜力和耐药性。然而，在 ES 中维持这种杂交表型的机制仍然难以捉摸。我们的研究提出了一个用于 ES 的逻辑 EMT 模型，强调了锌指 E 盒结合同源盒 2（ZEB2）、miR-145 和 miR-200 电路，这些电路维持着杂交状态。该模型与实验结果一致，并揭示了一个以前未知的支持间充质表型的电路。这些见解强调了 ZEB2 在 ES 中维持杂交状态的作用。
