MicroRNA-610 suppresses the proliferation of human glioblastoma cells by repressing CCND2 and AKT3

Abstract

Previous studies have shown that microRNA (miR)-610 is crucial in a variety of biological processes in various types of human cancer cells. However, the role of this microRNA in glioblastoma (GBM) is presently unclear. In this study, the role of miR-610 in cell proliferation was investigated in GBM. It was demonstrated that miR-610 expression is markedly downregulated in GBM cells and GBM tissues compared with normal human astrocytes (NHAs) and normal brain tissue, respectively. Ectopic expression of miR-610 reduced the proliferation and anchorage-independent growth of GBM cells, whereas inhibition of miR-610 promoted this effect. Bioinformatics analysis further revealed cyclin D2 (CCND2) and AKT3, putative tumor promoters, as potential targets of miR-610. Data from reporter assays showed that miR-610 directly binds to the 3'-untranslated region of CCND2 and AKT3 mRNA, and represses their expression at the transcriptional and translational levels. In conclusion, the data provide compelling evidence that miR-610 functions as an anti-onco-miRNA, which is important in inhibiting cell proliferation in GBM, and its anti-oncogenic effects are mediated chiefly through direct suppression of CCND2 and AKT3 expression.