microRNA-513c suppresses the proliferation of human glioblastoma cells by repressing low-density lipoprotein receptor-related protein 6

Abstract

Aberrant activation of the Wnt/β-catenin signaling pathway is frequently observed in glioblastoma (GBM) cells. Therefore, it was hypothesized that low-density lipoprotein receptor-related protein 6 (LRP6) may be involved in activating the Wnt/β-catenin pathway in the progression of GBM. The present study reported that the expression of microRNA (miR)-513c was markedly downregulated in GBM cells and GBM tissues compared with that in normal human astrocytes and normal brain tissues. Previous studies have demonstrated that miR-513c is critical in a variety of biological processes in various human cancer cells. The role of this miR in GBM cells was therefore investigated in the present study. Ectopic expression of miR-513c reduced the proliferation and anchorage-independent growth of GBM cells, whereas inhibition of miR-513c promoted this effect. Bioinformatic analysis further identified LRP6, a putative tumor suppressor, as a potential target of miR-513c. Luciferase reporter assays revealed that miR-513c directly bound to the 3'-untranslated region of LRP6 mRNA and repressed the expression at the transcriptional as well as the translational level. In functional assays, miR-513c suppressed GBM cell proliferation, which was reversed by an inhibitor of miR-513c. In conclusion, the present study provided compelling evidence that miR-513c functions as a tumor suppressor miRNA, which may be important in the inhibition of cell proliferation in GBM. In addition, the tumor suppressive effects were mediated predominantly through the direct suppression of the expression of LRP6.