Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis

• DOI: 10.1164/rccm.201610-2157oc
• Publication Date: 2017-08-30T14:56:57Z
• Authors: Asawari Korde; Lei Jin; Jian-ge Zhang; Anuradha Ramaswamy; Buqu Hu; Saeed Kolahian; Brenda Juan Guardela; Jose Herazo-Maya; Jill M. Siegfried; Laura Stabile; Margaret A. Pisani; Roy S. Herbst; Naftali Kaminski; Jack A. Elias; Jonathan T. Pucha...; Shervin S. Takyar
• Keywords: Mice, Knockout; Vascular Endothelial Growth Factor A; 0303 health sciences; Lung Neoplasms; Neovascularization, Pathologic; Endothelial Cells; Polymerase Chain Reaction; Survival Analysis; 3. Good health; Disease Models, Animal; Mice; MicroRNAs; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Animals; Lung

Vascular endothelial growth factor down-regulates microRNA-1 (miR-1) in the lung endothelium, and cells play a critical role tumor progression angiogenesis. To examine clinical significance of miR-1 non-small cell cancer (NSCLC) its specific endothelium. levels were measured by Taqman assay. Endothelial isolated magnetic sorting. We used vascular cadherin promoter to create vascular-specific lentiviral vector an inducible transgenic mouse. KRASG12D mut/Trp53-/- (KP) mice, lung-specific Lewis carcinoma xenografts, primary test effects miR-1. In two cohorts patients with NSCLC, lower tumors than cancer-free tissue. Tumor correlated overall survival NSCLC. also from NSCLC tumor-bearing lungs KP mouse model. examined testing overexpression. Vector-mediated delivery or overexpression decreased burden reduced vascularity tracheal angiogenesis mice. cells, level was regulated through phosphoinositide 3-kinase specifically controlled proliferation, de novo DNA synthesis, ERK1/2 activation. Myeloproliferative leukemia oncogene targeted endothelium is down-regulated controls