Chen Lei, Du Cheng, Wang Liang, Yang Chen, Zhang Jia-rui, Li Nan, Li Yi, Xie Xiao-Dong, Gao Guo-dong
Department of Neurosurgery, TangDu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, People's Republic of China.
Department of Oncology, General Hospital of Shenyang Military Region, Shenyang 110016, People's Republic of China.
J Neurol Sci. 2014 Nov 15;346(1-2):293-8. doi: 10.1016/j.jns.2014.09.014. Epub 2014 Sep 19.
Astrocytoma is the most common primary brain tumor and it is associated with poor prognosis. Accumulating evidences suggest that certain molecular abnormalities or genetic mutations are associated with its progression and prognosis. Human transcriptional coactivator 4 (PC4), originally identified as a transcriptional coactivator then as a DNA replication and repair factor has been shown to be involved in chromatin organization. Recently, it is reported to function both as tumor suppressor and promoter depending on the cellular settings. In the present study, we for the first time demonstrated that the expression of PC4 in astrocytoma was upregulated as assessed by western blot and immunohistochemical staining. Moreover, elevated PC4 expression was strongly correlated with the progression of astrocytoma. Furthermore, high PC4 expression was also associated with poor overall survival. Finally, in vitro study demonstrated that siRNA mediated PC4 downregulation significantly inhibited the proliferation and invasiveness of human glioma cells. These results suggested that PC4 might play a role in human astrocytoma progression and may be used as a novel indicator for the prognosis of astrocytoma patient.
星形细胞瘤是最常见的原发性脑肿瘤，且预后较差。越来越多的证据表明，某些分子异常或基因突变与其进展和预后相关。人类转录共激活因子4（PC4）最初被鉴定为转录共激活因子，后又被发现是一种DNA复制和修复因子，已被证明参与染色质组织。最近，据报道，根据细胞环境的不同，PC4既可以作为肿瘤抑制因子，也可以作为肿瘤促进因子发挥作用。在本研究中，我们首次通过蛋白质免疫印迹法和免疫组织化学染色评估发现，星形细胞瘤中PC4的表达上调。此外，PC4表达升高与星形细胞瘤的进展密切相关。此外，PC4高表达还与总体生存率低有关。最后，体外研究表明，siRNA介导的PC4下调显著抑制了人胶质瘤细胞的增殖和侵袭能力。这些结果表明，PC4可能在人类星形细胞瘤进展中发挥作用，并可能作为星形细胞瘤患者预后的一种新指标。
