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MicroRNA-503 acts as a tumor suppressor in glioblastoma for multiple antitumor effects by targeting IGF-1R

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microRNA (miRNA) dysregulation is associated with various types of human cancer by regulating cancer cell survival, proliferation and invasion. Aberrant expression of microRNA-503 (miR-503) has been reported in several cancer profiles. However, potential linkage of miR-503 levels and the underlying regulatory mechanisms in human glioblastoma multiforme (GBM) remain unclear. In the present study, we showed for the first time that the expression of miR-503 was significantly reduced in GBM tissues and cell lines (U251 and U87MG) relative to normal brain tissues. Furthermore, our results demonstrated that overexpression of miR-503 in GBM cell lines not only suppressed cell proliferation through inducing G0/G1 cell cycle arrest and apoptosis, but also inhibited cancer cell migration and tumor invasion. In addition, we identified insulin-like growth factor-1 (IGF1R) receptor mRNA is a bona fide target of miR-503 by computational analysis followed by luciferase reporter assays. Of note, upregulation of miR-503 in GBM cells suppressed endogenous IGF-1R protein expression. Further mechanistic analysis revealed that forced expression of miR-503 inhibited AKT activation, suggesting the tumor suppressive effect of miR-503 in GBM cells is partially mediated by phosphatidylinositol 3-kinase/AKT signaling. Taken together, the results of the present study demonstrated that miR-503 is a tumor suppressor for GBM and a favorable factor against glioma progression through targeting IGF-1R, thus providing a new evidence-supported prognostic marker for GBM diagnosis.
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Document Type: Research Article

Affiliations: 1: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China 2: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China 3: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China 4: Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA

Publication date: March 1, 2014

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