Overexpression of miR‑145 in U87 cells reduces glioma cell malignant phenotype and promotes survival after in vivo implantation

Yong Lu, Henry Ford Health System
Michael Chopp, Henry Ford Health System
Xuguang Zheng, Henry Ford Health System
Mark Katakowski, Henry Ford Health System
Ding Wang, Henry Ford Health System
Elise Fraser, Henry Ford Health System
Monique Nguyen, Henry Ford Health System
Feng Jiang, Henry Ford Health System

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.