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Published on: November 28, 2015
Tumor suppressor candidate gene, NDRG2 is frequently inactivated in human glioblastoma multiforme
Bin Zhou1, Zhuo Tang1, Yanchun Deng1
1Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Abstract:
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.
Insights
N-myc downstream regulated gene 2 (NDRG2) expression is reduced in human glioma, correlating negatively with tumor grade. Aberrant promoter methylation likely causes this NDRG2 downregulation, impacting glioma progression.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- N-myc downstream regulated gene 2 (NDRG2) is frequently downregulated in various cancers.
- Understanding NDRG2's role in glioma is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate NDRG2 expression in human glioma.
- To explore the relationship between NDRG2 expression and glioma grade.
- To elucidate the regulatory mechanisms, specifically promoter methylation, underlying NDRG2 downregulation in glioma.
Main Methods:
- Quantitative polymerase chain reaction (qPCR) for mRNA expression analysis.
- Immunohistochemistry and western blot for protein expression assessment.
- Bisulfite sequencing to determine NDRG2 promoter methylation status.
Main Results:
- NDRG2 mRNA and protein levels were significantly lower in glioma tissues compared to adjacent normal tissues.
- A significant negative correlation was observed between glioma tumor grade and NDRG2 expression.
- Glioma tissues exhibited a higher NDRG2 promoter methylation rate (46.3%) than normal tissues (18.2%).
Conclusions:
- NDRG2 expression is downregulated in human glioma, with levels inversely proportional to tumor grade.
- Aberrant methylation of the NDRG2 promoter region is a likely mechanism for its transcriptional inactivation in glioma.
- NDRG2 downregulation may contribute to glioma pathogenesis and progression.
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