Cullin1 regulates proliferation, migration and invasion of glioma cells
Cullin1 regulates proliferation, migration and invasion of glioma cells
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DOI：
10.1007/s12032-014-0227-x
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发表时间：
2014-10-01
期刊：
影响因子：
3.4
通讯作者：
Miao, FA-An
中科院分区：
文献类型：
--
作者：
Fan, Yue-Chao;Zhu, Yi-Shuo;Miao, FA-An
本研究旨在探讨Cullin 1（Cul 1）在人脑胶质瘤发病机制中的作用，以及Cul 1在胶质瘤细胞生长、迁移和侵袭中的作用。应用组织芯片和免疫组化技术检测191例胶质瘤组织、8例正常脑组织和8例癌旁正常脑组织中Cul 1的表达。利用特异性siRNA下调胶质母细胞瘤细胞Cul 1的表达，研究Cul 1表达下调对胶质瘤细胞增殖、侵袭和迁移的影响。结果表明，Cul 1在良恶性肿瘤组织中的表达均显著高于癌旁正常脑组织（P < 0.05）。我们没有发现Cul 1的表达和临床病理参数之间的任何相关性。此外，我们发现通过RNA干扰敲低Cul 1显著抑制细胞增殖并导致细胞周期停止。这种细胞增殖的减少是由于G1期阻滞，因为cyclinA、cyclinD 1和cyclinE减少，而p21和p27上调。Cul 1基因的沉默抑制了胶质瘤细胞的迁移和侵袭能力，MMP-2和MMP-9的表达下调在很大程度上降低了胶质瘤细胞的侵袭和迁移能力。Cul 1在人脑胶质瘤中的表达显著增加，可能参与胶质瘤细胞的增殖、迁移和侵袭。
This study was designed to explore the role of Cullin1 (Cul1) in the pathogenesis of human glioma and to investigate the role of Cul1 in the growth, migration and invasion of glioma cells. Expression of Cul1 in 191 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues was analyzed by tissue microarray and immunohistochemistry. Cul1 expression in human glioblastoma cells was knocked down by specific siRNA to study the effect of down-regulation of Cul1 on proliferation, invasion and migration of glioma cells. Our results showed that Cul1 expression increased significantly in tissues from the benign tumor and malignant tumor in comparison with those from the tumor-adjacent normal brain (P < 0.05 for both). We did not find any correlation between Cul1 expression and clinicopathological parameters. In addition, we found that knockdown of Cul1 by RNA interference markedly inhibited cell proliferation and caused cessation of cell cycle. This reduced cell proliferation was due to G1 phase arrest as cyclinA, cyclinD1 and cyclinE were diminished, whereas p21 and p27 were up-regulated. We further demonstrated that silencing of Cul1 in glioma cells inhibited the cell migration and invasion abilities, and down-regulation of MMP-2 and MMP-9 expression greatly contributed to the reduced cell invasion and migration abilities. Our data indicated that Cul1 expression significantly increased in human glioma, and it may be involved in proliferation, migration and invasion of glioma cells.