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


OBJECTIVE
We aimed to evaluate the methylation-mediated expression regulation of RUNX3 gene in brain tumors.


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).


CONCLUSIONS
This study overemphasized the RUNX3 gene importance in brain tumors, due to the existence of at least one methylated allele.
Department of Medical Biology, Ege University Medical Faculty, Bornova, 35100, Izmir, Turkey, cbavci@gmail.com.
C B
CB
Avci
Y
Y
Dodurga
S Y
SY
Susluer
Z O D
ZO
Sıgva
M
M
Yucebas
H O
HO
Caglar
T
T
Akalin
T
T
Dalbasti
N
N
Oktar
C
C
Gunduz
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D050677:Core Binding Factor Alpha 3 Subunit; D012334:RNA, Neoplasm