Abstract
Purpose of Review: It has been known for decades that in order to grow, tumors need to activate quiescent endothelial cells to form a functional vascular network, a process termed 'angiogenesis'. However, the molecular determinants that reverse this endothelial quiescence to facilitate pathological angiogenesis are not yet completely understood. This review examines a critical regulatory switch at the level of Ras that activates this angiogenic switch process and the role that microRNAs play in this process. Recent Findings: In the last few years, microRNAs, a new class of small RNA molecules, have emerged as key regulators of several cellular processes, including angiogenesis. MicroRNAs such as miR-126, miR-296, and miR-92a have been shown to play important roles in angiogenesis. We recently described how miR-132, an angiogenic growth factor inducible microRNA in the endothelium, facilitates pathological angiogenesis by downregulating p120RasGAP, a molecular brake for Ras. Importantly, targeting miR-132 with a complementary, synthetic antimicroRNA restored the brake and decreased angiogenesis and tumor burden in multiple tumor models. Taken together, emerging evidence suggests a central role for microRNAs downstream of multiple growth factors in regulating endothelial proliferation, migration, and vascular patterning. Summary: Further research into miR-132-p120RasGAP biology and more broadly, microRNA regulation of Ras pathways in the endothelium will not only advance our understanding of angiogenesis but also provide opportunities for therapeutic intervention.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 171-176 |
| Number of pages | 6 |
| Journal | Current Opinion in Hematology |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 2011 |
| Externally published | Yes |
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Keywords
- endothelial quiescence
- microRNA-132
- p120RasGAP
- pathological angiogenesis
ASJC Scopus subject areas
- Hematology
Cite this
MicroRNA-mediated regulation of the angiogenic switch. / Anand, Sudarshan; Cheresh, David A.
In: Current Opinion in Hematology, Vol. 18, No. 3, 05.2011, p. 171-176.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-mediated regulation of the angiogenic switch
AU - Anand, Sudarshan
AU - Cheresh, David A.
PY - 2011/5
Y1 - 2011/5
N2 - Purpose of Review: It has been known for decades that in order to grow, tumors need to activate quiescent endothelial cells to form a functional vascular network, a process termed 'angiogenesis'. However, the molecular determinants that reverse this endothelial quiescence to facilitate pathological angiogenesis are not yet completely understood. This review examines a critical regulatory switch at the level of Ras that activates this angiogenic switch process and the role that microRNAs play in this process. Recent Findings: In the last few years, microRNAs, a new class of small RNA molecules, have emerged as key regulators of several cellular processes, including angiogenesis. MicroRNAs such as miR-126, miR-296, and miR-92a have been shown to play important roles in angiogenesis. We recently described how miR-132, an angiogenic growth factor inducible microRNA in the endothelium, facilitates pathological angiogenesis by downregulating p120RasGAP, a molecular brake for Ras. Importantly, targeting miR-132 with a complementary, synthetic antimicroRNA restored the brake and decreased angiogenesis and tumor burden in multiple tumor models. Taken together, emerging evidence suggests a central role for microRNAs downstream of multiple growth factors in regulating endothelial proliferation, migration, and vascular patterning. Summary: Further research into miR-132-p120RasGAP biology and more broadly, microRNA regulation of Ras pathways in the endothelium will not only advance our understanding of angiogenesis but also provide opportunities for therapeutic intervention.
AB - Purpose of Review: It has been known for decades that in order to grow, tumors need to activate quiescent endothelial cells to form a functional vascular network, a process termed 'angiogenesis'. However, the molecular determinants that reverse this endothelial quiescence to facilitate pathological angiogenesis are not yet completely understood. This review examines a critical regulatory switch at the level of Ras that activates this angiogenic switch process and the role that microRNAs play in this process. Recent Findings: In the last few years, microRNAs, a new class of small RNA molecules, have emerged as key regulators of several cellular processes, including angiogenesis. MicroRNAs such as miR-126, miR-296, and miR-92a have been shown to play important roles in angiogenesis. We recently described how miR-132, an angiogenic growth factor inducible microRNA in the endothelium, facilitates pathological angiogenesis by downregulating p120RasGAP, a molecular brake for Ras. Importantly, targeting miR-132 with a complementary, synthetic antimicroRNA restored the brake and decreased angiogenesis and tumor burden in multiple tumor models. Taken together, emerging evidence suggests a central role for microRNAs downstream of multiple growth factors in regulating endothelial proliferation, migration, and vascular patterning. Summary: Further research into miR-132-p120RasGAP biology and more broadly, microRNA regulation of Ras pathways in the endothelium will not only advance our understanding of angiogenesis but also provide opportunities for therapeutic intervention.
KW - endothelial quiescence
KW - microRNA-132
KW - p120RasGAP
KW - pathological angiogenesis
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UR - http://www.scopus.com/inward/citedby.url?scp=79955001308&partnerID=8YFLogxK
U2 - 10.1097/MOH.0b013e328345a180
DO - 10.1097/MOH.0b013e328345a180
M3 - Article
C2 - 21423013
AN - SCOPUS:79955001308
VL - 18
SP - 171
EP - 176
JO - Current Opinion in Hematology
JF - Current Opinion in Hematology
SN - 1065-6251
IS - 3
ER -