A TARBP2-Dependent miRNA Expression Profile Underlies Cancer Stem Cell Properties and Provides Candidate Therapeutic Reagents in Ewing Sarcoma

详细信息	查看全文 | 推荐本文 |

• 作者：Claudio De&#160 ; Vito¹ ; ³ ; Nicolo Riggi¹ ; ³ ; Sandrine Cornaz¹ ; Mario-Luca Suvà ; ¹ ; Karine Baumer¹ ; Paolo Provero² ; Ivan Stamenkovic¹ ; ^{ivan.stamenkovic@chuv.ch}
• 刊名：Cancer Cell
• 出版年：2012
• 期刊代码：43_15356108
• 类别：med
• 出版时间：12 June, 2012
• 卷：21
• 期：6
• 页码：807-821
• 文件大小：1718 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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聽vivo. Our observations suggest that CSC self-renewal and tumor maintenance may depend on deregulation of TARBP2-dependent miRNA expression.