MiR-29c inhibits glioma cell proliferation, migration, invasion and angiogenesis
MiR-29c inhibits glioma cell proliferation, migration, invasion and angiogenesis
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DOI：
10.1007/s11060-013-1223-2
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发表时间：
2013-11-01
影响因子：
3.9
通讯作者：
Li, Zhong-lin
中科院分区：
文献类型：
--
作者：
Fan, Yue-chao;Mei, Peng-jin;Li, Zhong-lin
先前的研究报告称，miR-29c 在多种肿瘤中显着下调。然而，人们对 miR-29c 在人类神经胶质瘤中的作用和分子机制知之甚少。使用定量 RT-PCR，我们证明与正常人星形胶质细胞和匹配的非肿瘤相关组织相比，miR-29c 在神经胶质瘤细胞系和人原发性神经胶质瘤组织中显着下调（P < 0.05，chi(2) 检验）。 miR-29c 的过度表达显着降低增殖并导致细胞周期停止。细胞增殖减少是由于 G1 期停滞所致，因为细胞周期蛋白 D1 和细胞周期蛋白 E 减少，而 p27 和 p21 上调。我们进一步证明，miR-29c 过表达通过靶向 MMP-2 抑制胶质瘤细胞的迁移和侵袭能力。此外，我们还发现miR-29c的过表达会急剧抑制血管生成，这与VEGF的下调相关。数据表明miR-29c可能是参与神经胶质瘤进展的肿瘤抑制因子。
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, chi(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.