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 down-regulation 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.
Highlights
High-grade gliomas are malignant as they are highly vascularized and invasive, and characterized by high incidence of recurrence and poor prognosis [1,2]
Our present study demonstrates that overexpression of miR‐145 inhibits glioma cell proliferation, invasion, angiogenesis in vitro, and decreases glioma cell growth in an animal model, possibly through the mechanism of miR‐145-related decrease of ADAM17 and epidermal growth factor receptor (EGFR) protein expressions via the Erk/p-Erk pathway in U87 cells
The data suggested that stable transfection of miR‐145 and zip‐145 was established in the U87 cell lines
Summary
High-grade gliomas are malignant as they are highly vascularized and invasive, and characterized by high incidence of recurrence and poor prognosis [1,2]. The prognosis for patients with malignant gliomas has not significantly changed in recent years [3]. Glioma cells infiltrate into the normal brain adjacent to the tumor causing treatment failure from conventional Malignant gliomas are highly fatal and often strike patients in their most productive years
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