Previous studies reported that miR-29c is significantly downregulated in several tumors. However, little is known about the effect and molecular mechanisms of action of miR-29c in human glioma. Using quantitative RT-PCR, we demonstrated that miR-29c was significantly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues (P < 0.05, χ(2) test). Overexpression of miR-29c dramatically reduced the proliferation and caused cessation of cell cycle. The reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 and p21 are upregulated. We further demonstrated that miR-29c overexpression suppressed the glioma cell migration and invasion abilities by targeting MMP-2. In addition, we also found that overexpression of miR-29c sharply inhibited angiogenesis, which correlated with down-regulation of VEGF. The data indicate that miR-29c may be a tumor suppressor involved in the progression of glioma.