Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Brain Res. 2013 Jul 3;1520:15-22. doi: 10.1016/j.brainres.2013.04.061. Epub 2013 May 15.
Glioma is an aggressive cancer with high mortality, especially in children. It is known that histone modification plays an important role in the pathogenesis of various cancers. However, it is unknown whether histone deacetylase 3 (HDAC3) plays a role in the tumorigenesis of children gliomas. This study was aimed to explore the potential effects of HDAC3 in children gliomas. Expression of HDAC3 was measured in children glioma samples (n=70) and normal brain tissues (n=7) by real-time PCR and western blotting. Survival of the two groups was analyzed by the Kaplan-Meier method. The effects of HDAC3 in the pathogenesis of gliomas were analyzed by silencing the glioma cells U87-MG and U251. Data showed that HDAC3 was significantly elevated in children's gliomas, following the glioma grade, with almost no expression in normal brain tissues. Ectopic HDAC3 expression was correlated with poorer prognosis of children with glioma. In glioma cell lines, inhibition of HDAC3 using siRNA could suppress proliferation and sphere formation, induce G0/G1 arrest and apoptosis, and suppress the migration of glioma cells in comparison with controls. The higher level of HDAC3 expression was associated with more advanced tumor grades and shorter survival. HDAC3 participated in the pathogenesis of children gliomas by promoting glioma cell proliferation and migration.
神经胶质瘤是一种死亡率很高的侵袭性癌症，尤其是在儿童中。已知组蛋白修饰在各种癌症的发病机制中起着重要作用。然而，组蛋白去乙酰化酶 3（HDAC3）是否在儿童神经胶质瘤的发生中起作用尚不清楚。本研究旨在探讨 HDAC3 在儿童神经胶质瘤发病机制中的潜在作用。通过实时 PCR 和 Western blot 测定 70 例儿童神经胶质瘤样本（n=70）和 7 例正常脑组织（n=7）中 HDAC3 的表达。通过 Kaplan-Meier 方法分析两组的生存情况。通过沉默神经胶质瘤细胞 U87-MG 和 U251 分析 HDAC3 在胶质瘤发病机制中的作用。结果显示，HDAC3 在儿童神经胶质瘤中显著升高，随胶质瘤分级升高，在正常脑组织中几乎不表达。异位 HDAC3 表达与儿童神经胶质瘤预后不良相关。在神经胶质瘤细胞系中，与对照组相比，使用 siRNA 抑制 HDAC3 可抑制增殖和球体形成，诱导 G0/G1 期阻滞和细胞凋亡，并抑制神经胶质瘤细胞的迁移。HDAC3 表达水平越高，肿瘤分级越高，生存时间越短。HDAC3 通过促进神经胶质瘤细胞的增殖和迁移参与儿童神经胶质瘤的发病机制。
