title: Overexpression of miR‑145 in U87 cells reduces glioma cell malignant phenotype and promotes survival after in vivo implantation.
abstract: In the present study, we sought to elucidate the effect of miR‑145 on glioma cell progression and its mechanisms of action. We examined the effects of miR‑145 on proliferation and invasion of U87 glioma cells and on capillary tube formation. Our data show that restoration of miR‑145 in U87 glioma cells significantly reduced their in vitro proliferation, invasion and angiogenesis. However, decreased miR‑145 expression promoted U87 glioma cell proliferation, invasion and angiogenesis, and reduced-expression of miR‑145 increased ADAM17 and EGFR expression in U87 cells. Overexpression of miR‑145 reduced ADAM17 and EGFR expression. VEGF secretion and VEGF expression were decreased by increased miR‑145 expression in U87 cells and were reversed by miR‑145 downregulation in vitro. Nude mice with intracerebral implantation of U87 overexpressing miR‑145 cells exhibited significantly reduced tumor growth and promoted survival compared with control groups. Taken together, these results suggest a role for miR‑145 as a tumor suppressor which inhibits glioma cell proliferation, invasion and angiogenesis in vitro and reduces glioma growth in vivo.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Katakowski
authors.affiliation: Department of Hematology/Oncology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Fraser
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Monique
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse