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Updated: May 20, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells
Prue N Plummer1, Ruth Freeman, Ryan J Taft
1School of Medical Science, Griffith University, Parklands Dr, Gold Coast, Australia.
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.
Insights
MicroRNAs (miRNAs) are crucial for tumor angiogenesis. Targeting specific miRNAs, like miR-10b and miR-196b, in bone marrow-derived endothelial progenitor cells (EPCs) suppresses tumor growth by inhibiting angiogenesis.
Area of Science:
- Molecular Biology
- Cancer Research
- Angiogenesis
Background:
- Bone marrow-derived endothelial progenitor cells (EPCs) are vital for tumor angiogenesis.
- MicroRNAs (miRNAs) regulate cellular processes, but their role in bone marrow-mediated angiogenesis was unclear.
Purpose of the Study:
- To investigate the role of miRNAs in bone marrow-derived EPCs in regulating angiogenesis and tumor growth.
- To identify specific miRNAs involved in this process and evaluate their therapeutic potential.
Main Methods:
- Genetic ablation of Dicer in bone marrow-derived cells in mice.
- Genome-wide deep sequencing of small RNAs from tumor EPCs.
- In vivo targeting of specific miRNAs (miR-10b, miR-196b) in mouse tumor models.
Main Results:
- Ablation of Dicer in bone marrow decreased circulating EPCs, suppressed angiogenesis, and impaired tumor growth.
- miR-10b and miR-196b were identified as key intrinsic miRNAs in tumor EPCs.
- Elevated expression of miR-10b and miR-196b was observed in human breast tumor vasculature.
- Targeting miR-10b and miR-196b significantly inhibited angiogenesis-dependent tumor growth.
Conclusions:
- Bone marrow-derived miRNAs, specifically miR-10b and miR-196b, play a critical role in regulating angiogenesis and tumor growth.
- Targeting these miRNAs presents a potential novel therapeutic strategy for inhibiting tumor angiogenesis.
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