Zhou Bin, Tang Zhuo, Deng Yanchun, Hou Shuangxing, Liu Nan, Lin Wei, Liu Xinping, Yao Libo
Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Neurosurgery, Xijing Hospital Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Mol Med Rep. 2014 Aug;10(2):891-6. doi: 10.3892/mmr.2014.2237. Epub 2014 May 14.
N‑myc downstream regulated gene 2 (NDRG2) is highly expressed in numerous normal tissues, while it is marginally expressed or undetectable in various tumors, including lung and colon cancer. In order to investigate the expression of NDRG2 in human glioma and its downstream regulatory mechanisms, quantitative polymerase chain reaction (qPCR), immunohistochemistry and western blot analyses were used to assess NDRG2 mRNA and protein expression in different grades of human glioma and adjacent normal tissues. The methylation status of the NDRG2 promoter region was also determined using bisulfite sequencing. NDRG2 mRNA expression was observed to be significantly lower in glioma tissues than in adjacent normal tissues (P<0.05). Furthermore, a significant negative correlation was found between the glioma tumor grade and NDRG2 expression (P<0.05), at the mRNA and protein levels. Moreover, the methylation rate of the NDRG2 promoter region was 46.3% in the glioma tissues compared with 18.2% in the adjacent normal tissues (P<0.05). These findings show that NDRG2 expression is downregulated in human glioma and that the level of NDRG2 expression negatively correlates with the glioma grade. Furthermore, these findings indicate that NDRG2 downregulation may be due to aberrant methylation of the NDRG2 promoter region and subsequent transcriptional inactivation.
N- myc下游调控基因2(NDRG2)在许多正常组织中高表达,而在包括肺癌和结肠癌在内的各种肿瘤中表达微弱或无法检测到。为了研究NDRG2在人类胶质瘤中的表达及其下游调控机制,采用定量聚合酶链反应(qPCR)、免疫组织化学和蛋白质印迹分析来评估不同级别人类胶质瘤及相邻正常组织中NDRG2 mRNA和蛋白质的表达。还使用亚硫酸氢盐测序法测定了NDRG2启动子区域的甲基化状态。结果观察到,胶质瘤组织中NDRG2 mRNA表达明显低于相邻正常组织(P<0.05)。此外,在mRNA和蛋白质水平上,胶质瘤肿瘤分级与NDRG2表达之间存在显著负相关(P<0.05)。而且,胶质瘤组织中NDRG2启动子区域的甲基化率为46.3%,而相邻正常组织中为18.2%(P<0.05)。这些发现表明,NDRG2在人类胶质瘤中表达下调,且NDRG2表达水平与胶质瘤分级呈负相关。此外,这些发现表明NDRG2下调可能是由于NDRG2启动子区域异常甲基化及随后的转录失活所致。