title: The synergistic regulation of VEGF-mediated angiogenesis through miR-190 and target genes.
abstract: VEGF is a major contributor to angiogenesis, a vital process in normal growth and development and tumor transition. However, the current clinical efficacy of VEGF inhibitors is limited, and the molecular mechanism underlying VEGF regulation remains to be elucidated. Here we show that miR-190 directly targets a group of angiogenic effectors besides VEGF per se. Noted, these effectors can transcriptionally regulate VEGF expression in an intracellular or intercellular manner, thus demonstrating that miR-190 modulates the VEGF-mediated tumor angiogenesis at three levels. The synergistic effect of miR-190 and its target genes demonstrates a complex but apparently more stable system, allowing for the tight control of the level of VEGF. Finally, we showed that miR-190 significantly suppresses tumor metastasis, especially angiogenesis. Together, these results indicate that miR-190 is a promising antitumor target in clinical applications.
authors: Biomedical Engineering Department, College of Engineering, Peking University, Beijing 100871, China.
authors: Yang
authors: Y
authors: Hao
authors: Biomedical Engineering Department, College of Engineering, Peking University, Beijing 100871, China.
authors: Junyu
authors: J
authors: Yang
authors: Biomedical Engineering Department, College of Engineering, Peking University, Beijing 100871, China.
authors: Shenyi
authors: S
authors: Yin
authors: Biomedical Engineering Department, College of Engineering, Peking University, Beijing 100871, China.
authors: Hanshuo
authors: H
authors: Zhang
authors: Biomedical Engineering Department, College of Engineering, Peking University, Beijing 100871, China.
authors: Yu
authors: Y
authors: Fan
authors: Biomedical Engineering Department, College of Engineering, Peking University, Beijing 100871, China.
authors: Changhong
authors: C
authors: Sun
authors: Peking University School of Oncology, Beijing Cancer Hospital, Beijing 100142, China.
authors: Jin
authors: J
authors: Gu
authors: Biomedical Engineering Department, College of Engineering, Peking University, Beijing 100871, China State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors: Jianzhong Jeff
authors: JJ
authors: Xi
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism*; D019655:Quantitative Trait, Heritable; D034622:RNA Interference; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C576613:MIRN190 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF; angiogenesis; metastasis; miR-190; synergistic effect