Promoter hypermethylation-mediated down-regulation of RUNX3 gene in human brain tumors

• Published in: Irish journal of medical science Vol. 183; no. 2; pp. 259 - 264
• Main Authors: Avci, C. B., Dodurga, Y., Susluer, S. Y., Sıgva, Z. O. D., Yucebas, M., Caglar, H. O., Akalin, T., Dalbasti, T., Oktar, N., Gunduz, C.
• Format: Journal Article
• Language: English
• Published: London Springer London 01-06-2014
• Subjects: Adult; Aged; Astrocytoma - genetics; Brain Neoplasms - genetics; Cell Line, Tumor; Core Binding Factor Alpha 3 Subunit - genetics; DNA Methylation - genetics; Down-Regulation - genetics; Family Medicine; Female; Gene Expression Regulation, Neoplastic; General Practice; Glioblastoma - genetics; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Meningeal Neoplasms - genetics; Meningioma - genetics; Middle Aged; Original Article; Promoter Regions, Genetic - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - genetics; Young Adult; DNA methylation; Gene expression; Human brain tumors
• ISSN: 0021-1265; 1863-4362
• DOI: 10.1007/s11845-013-1001-3

Background
The Runx family proteins, including
RUNX3
, are tissue-restricted transcription factors and play role in neuronal development and tumorigenesis.
RUNX3
has an important role in glioblastoma (GBM) tumorigenesis because of its promoter hypermethylation.
Aim
We aimed to evaluate the methylation-mediated expression regulation of
RUNX3
gene in brain tumors.
Patients and methods
Cases of meningiomas WHO grade III (3), anaplastic astrocytomas (3), diffuse astrocytoma (3), and GBM (12) were recruited into this study. Real-time quantitative PCR was performed for analyses of DNA promoter methylation and analyses of methylation-mediated expression status of
RUNX3
gene was performed by real-time quantitative RT-PCR.
Results
There was no significant difference between methylated and unmethylated quantitative ratio of
RUNX3
gene promoter region and also no significant difference in relative ratio of
RUNX3
gene expression in brain tumor groups. Methylated and unmethylated ratio in anaplastic astrocytoma, diffuse astrocytoma, GBM, meningioma (WHO grade III) and in all groups were; 1.44, 1.09, 1.51, 1.52 and 1.43, respectively. One allele was found methylated necessarily. No methylation was detected in one case of GBM group and one case of anaplastic astrocytoma group. There was no unmethylated promoter in one of the GBM cases. There were significant differences between relative ratio of
RUNX3
gene expression and methylated/unmethylated ratio rates for all cases (
p
 = 0.001) and GBM groups (
p
 = 0.041).
Conclusion
This study overemphasized the
RUNX3
gene importance in brain tumors, due to the existence of at least one methylated allele.