Angiogenesis regulation by the miR-17-92 cluster. The polycistronic miR-17-92 cluster encodes 6 mature miRNAs: miR17, miR18a, miR-19a, miR-20a, miR-19b, and miR-92a, all processed from a single primary transcript. miR-18a/19 directly repress the expression of the antiangiogenic, secreted molecules thrombospondin-1 (Tsp-1) and connective tissue growth factor in tumor cells, thereby promoting angiogenesis in the adjacent tumor endothelium by a paracrine, cell-nonautonomous mechanism. Conversely, miR-17/20 and miR-92a cell-autonomously target Janus kinase 1 (Jak1) and integrin α5 (Itgα5) in endothelial cells, thus negatively regulating endothelial cell sprouting and vascular morphogenesis. The miR-17-92 cluster miRNAs also repress targets in tumor cells that promote proliferation and survival (Pten, Bim, p21); these relationships are simplified for purposes of this schematic. Professional illustration by Marie Dauenheimer.