MicroRNAs Regulate Tumor Angiogenesis Modulated by Endothelial Progenitor Cells

Plummer, P. N., Freeman, R., Taft, R. J., Vider, J., Sax, M., Umer, B. A., Gao, D. C., Johns, C., Mattick, J. S., Wilto, S. D., Ferro, V., McMillan, N. A. J., Swarbrick, A., Mittal, V., Mellick, A. S. (January 2013) MicroRNAs Regulate Tumor Angiogenesis Modulated by Endothelial Progenitor Cells. Cancer Research, 73 (1). pp. 341-352. ISSN 0008-5472

URL: http://www.ncbi.nlm.nih.gov/pubmed/22836757
DOI: 10.1158/0008-5472.can-12-0271

Abstract

Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth factor stimulation and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis. Cancer Res; 73(1); 341-52. (C)2012 AACR.

Item Type: Paper
Uncontrolled Keywords: breast-cancer gene-expression immune-system metastasis growth dicer receptor neovascularization suppressor inhibitor
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:
Communities: CSHL labs > Gingeras lab
Depositing User: Matt Covey
Date: 1 January 2013
Date Deposited: 08 Feb 2013 18:50
Last Modified: 08 Feb 2013 18:50
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27232

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