Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Cancer Cell. 2012 Jun 12;21(6):807-21. doi: 10.1016/j.ccr.2012.04.023.
We have recently demonstrated that human pediatric mesenchymal stem cells can be reprogrammed toward a Ewing sarcoma family tumor (ESFT) cancer stem cell (CSC) phenotype by mechanisms that implicate microRNAs (miRNAs). Here, we show that the miRNA profile of ESFT CSCs is shared by embryonic stem cells and CSCs from divergent tumor types. We also provide evidence that the miRNA profile of ESFT CSCs is the result of reversible disruption of TARBP2-dependent miRNA maturation. Restoration of TARBP2 activity and systemic delivery of synthetic forms of either of two of its targets, miRNA-143 or miRNA-145, inhibited ESFT CSC clonogenicity and tumor growth in vivo. Our observations suggest that CSC self-renewal and tumor maintenance may depend on deregulation of TARBP2-dependent miRNA expression.
我们最近的研究表明，人类小儿间充质干细胞可以通过涉及 microRNAs (miRNAs) 的机制被重编程为尤文肉瘤家族肿瘤 (ESFT) 癌症干细胞 (CSC) 表型。在这里，我们表明 ESFT CSCs 的 miRNA 谱与胚胎干细胞和来自不同肿瘤类型的 CSCs 共享。我们还提供证据表明，ESFT CSCs 的 miRNA 谱是 TARBP2 依赖性 miRNA 成熟的可逆破坏的结果。TARBP2 活性的恢复和两种其靶标之一，miRNA-143 或 miRNA-145 的合成形式的系统递送，抑制了 ESFT CSC 的集落形成能力和体内肿瘤生长。我们的观察表明，CSC 自我更新和肿瘤维持可能依赖于 TARBP2 依赖性 miRNA 表达的失调。
