MicroRNA-mediated regulation of the angiogenic switch

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.

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.

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.