Abstract
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Cells, Cultured
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Child
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Child, Preschool
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Embryonic Stem Cells / metabolism
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Female
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Gene Expression Profiling*
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Gene Expression Regulation, Neoplastic
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Humans
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Induced Pluripotent Stem Cells / metabolism
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Male
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Mesenchymal Stem Cells / metabolism
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Mice
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Mice, Inbred NOD
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Mice, Knockout
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Mice, SCID
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MicroRNAs / genetics*
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Mutation
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sarcoma, Ewing / genetics
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Sarcoma, Ewing / pathology
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Sarcoma, Ewing / therapy
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Transplantation, Heterologous
Substances
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MicroRNAs
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RNA-Binding Proteins
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trans-activation responsive RNA-binding protein