MicroRNA-mediated regulation of the angiogenic switch.

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.

• Authors: Sudarshan Anand, David A Cheresh
• Journal: Current opinion in hematology (Curr Opin Hematol) Vol. 18 Issue 3 Pg. 171-6 (May 2011) ISSN: 1531-7048 [Electronic] United States
• PMID: 21423013 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• MicroRNAs

Topics

• Animals
• Endothelium, Vascular (metabolism)
• Humans
• MicroRNAs (genetics, metabolism)
• Neovascularization, Pathologic (genetics)