Cha S.-T.Chen P.-S.Johansson G.CHIA-YU CHUWang M.-Y.YUNG-MING JENGSUNG-LIANG YUJIN-SHING CHENKING-JEN CHANGJee S.-H.CHING-TING TANMING-TSAN LINKuo M.-L.2019-12-042019-12-0420100008-5472https://www.scopus.com/inward/record.uri?eid=2-s2.0-77950799838&doi=10.1158%2f0008-5472.CAN-09-2448&partnerID=40&md5=2b8812c35bf5226ba183a0790f007498https://scholars.lib.ntu.edu.tw/handle/123456789/434939Hypoxia-inducible factor-1α (HIF-1α) is widely considered to be one of the key regulators of tumor angiogenesis. The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia Herein, we have identified miR-519c as a hypoxia-independent regulator of HIF-1α, acting through direct binding to the HIF-1α 3' untranslated region and leading to reduced tumor angiogenesis. Overexpression of miR-519c resulted in a significant decrease of HIF-1α protein levels and reduced the tube formation of human umbilical vein endothelial cells; similarly, antagomir inhibition of miR-519c increased the level of HIF-1α protein and enhanced angiogenic activity, suggesting an important role of miR-519c in HIF-1α-mediated angiogenesis. Consistent with the overexpression of miR-519c in cancer patients with better prognosis, mice injected with miR-519c-overexpressing cells exhibited dramatically reduced HIF-1α levels, followed by suppressed tumor angiogenesis, growth, and metastasis. In addition, we found that hepatocyte growth factor (HGF), a known HIF-1α inducer, reduced the miR-519c levels through an Akt-dependent pathway. This regulation was posttranscriptional and may be mediated by suppression of miR-519c maturation. Taken together, our findings provide the first evidence that miR-519c is a pivotal regulator of tumor angiogenesis and that microenvironmental HGF contributes to regulating miR-519c biogenesis in cancer cells. ?2010 American Association for Cancer Research.[SDGs]SDG3hypoxia inducible factor 1alpha; micro rna 519c; microRNA; scatter factor; unclassified drug; 3' untranslated region; angiogenesis; animal experiment; animal model; animal tissue; article; controlled study; endothelium cell; male; metastasis; mouse; nonhuman; priority journal; prognosis; tumor angiogenesis; umbilical veinjournal article10.1158/0008-5472.CAN-09-2448202338792-s2.0-77950799838