Division of Neurosurgery, Department of Surgery, City of Hope National Medical Center, Duarte, California, United States of America.
PLoS One. 2013 Nov 15;8(11):e80970. doi: 10.1371/journal.pone.0080970. eCollection 2013.
The Polycomb group (PcG) proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM). By systematically interrogating The Cancer Genome Atlas (TCGA), we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy.
多梳抑制复合物（PcG）蛋白在组蛋白介导的表观遗传学中发挥着关键作用，这与胶质母细胞瘤（GBM）的恶性演变有关。通过系统地分析癌症基因组图谱（TCGA），我们发现与正常大脑相比，GBM 样本中 PcG 成员的表达普遍异常。最显著的差异是 EZH2、PHF19、CBX8 和 PHC2 的上调，以及 CBX7、CBX6、EZH1 和 RYBP 的下调。有趣的是，随着星形细胞瘤级别的增加，EZH2、PHF19、CBX7、CBX6 和 EZH1 的变化逐渐发生。我们通过 Western blot 和 qRT-PCR 验证了 CBX6、CBX7、CBX8 和 EZH2 在 GBM 细胞系中的异常表达，并通过免疫组织化学染色进一步验证了 CBX6 在 GBM 组织样本中的异常表达。为了确定 CBX6 在 GBM 中水平降低是否具有功能意义，我们在 GBM 细胞中过表达 CBX6，导致增殖能力下降。总之，GBM 中 PcG 蛋白的异常表达可能在恶性肿瘤的发生或维持中发挥作用。
