MicroRNA-mediated regulation of the angiogenic switch

被引:64
作者
Anand, Sudarshan
Cheresh, David A. [1 ,2 ]
机构
[1] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
endothelial quiescence; microRNA-132; p120RasGAP; pathological angiogenesis; GTPASE-ACTIVATING PROTEIN; HUMAN ENDOTHELIAL-CELLS; CARDIAC-HYPERTROPHY; VASCULAR INTEGRITY; MICE; EXPRESSION; PHENOTYPE; GROWTH; DICER; VEGF;
D O I
10.1097/MOH.0b013e328345a180
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:171 / 176
页数:6
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