Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, China,
J Neurooncol. 2013 Nov;115(2):179-88. doi: 10.1007/s11060-013-1223-2. Epub 2013 Aug 13.
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.
先前的研究表明，miR-29c 在多种肿瘤中显著下调。然而，miR-29c 在人胶质瘤中的作用及其分子机制知之甚少。通过定量 RT-PCR，我们发现与正常人星形胶质细胞和配对的非肿瘤相关组织相比，miR-29c 在胶质瘤细胞系和人原发性胶质瘤组织中显著下调（P < 0.05，卡方检验）。miR-29c 的过表达显著降低了增殖并导致细胞周期停滞。细胞增殖减少是由于细胞周期蛋白 D1 和细胞周期蛋白 E 减少，而 p27 和 p21 上调导致 G1 期阻滞。我们进一步证明，miR-29c 通过靶向 MMP-2 过表达抑制了胶质瘤细胞的迁移和侵袭能力。此外，我们还发现 miR-29c 的过表达明显抑制了血管生成，这与 VEGF 的下调有关。数据表明，miR-29c 可能是一种参与胶质瘤进展的肿瘤抑制因子。
