Tumor suppressor candidate gene, NDRG2 is frequently inactivated in human glioblastoma multiforme.

Abstract

N‑myc downstream regulated gene2 (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.