MicroRNA-mediated regulation of the angiogenic switch.
MicroRNA-mediated regulation of the angiogenic switch.
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DOI：
10.1097/moh.0b013e328345a180
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发表时间：
2011-05
影响因子：
3.2
通讯作者：
Cheresh DA
中科院分区：
文献类型：
--
作者：
Anand S;Cheresh DA
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 anti-microRNA 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.
