MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells

P.N. Plummer; R. Freeman; R.J. Taft; J. Vider; M. Sax; B.A. Umer; D. Gao; C Johns; J.S. Mattick; S.D. Wilton; V. Ferro; N.A.J. McMillan; A. Swarbrick; V. Mittal; A.S. Mellick

doi:10.1158/0008-5472.CAN-12-0271

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MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells

Journal article

Peer reviewed

MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells

P.N. Plummer, R. Freeman, R.J. Taft, J. Vider, M. Sax, B.A. Umer, D. Gao, C Johns, J.S. Mattick, S.D. Wilton, …

Cancer Research, Vol.73(1), pp.341-352

2013

DOI: https://doi.org/10.1158/0008-5472.CAN-12-0271

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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.

Details

Title: MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells
Authors/Creators: P.N. Plummer (Author/Creator) - Griffith University
R. Freeman (Author/Creator) - Griffith University
R.J. Taft (Author/Creator) - The University of Queensland
J. Vider (Author/Creator) - Griffith University
M. Sax (Author/Creator) - Griffith University
B.A. Umer (Author/Creator) - Griffith University
D. Gao (Author/Creator) - Cornell University
C Johns (Author/Creator) - Cold Spring Harbor Laboratory
J.S. Mattick (Author/Creator) - The University of Queensland
S.D. Wilton (Author/Creator) - Centre for Neuromuscular and Neurological Disorders
V. Ferro (Author/Creator) - The University of Queensland
N.A.J. McMillan (Author/Creator) - Griffith University
A. Swarbrick (Author/Creator) - Garvan Institute of Medical Research
V. Mittal (Author/Creator) - Houston Methodist
A.S. Mellick (Author/Creator) - Griffith University
Publication Details: Cancer Research, Vol.73(1), pp.341-352
Publisher: American Association for Cancer Research
Identifiers: 991005542823607891
Copyright: © 2012 American Association for Cancer Research
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.196 Micro & Long Noncoding RNA; 1.196.68 MicroRNA in Cancer
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine