TY - JOUR
TI - Differential and Common Signatures of miRNA Expression and Methylation
in Childhood Central Nervous System Malignancies: An Experimental and
Computational Approach
AU - Lambrou, I, George
AU - Poulou, Myrto
AU - Giannikou, Krinio and
AU - Themistocleous, Marios
AU - Zaravinos, Apostolos
AU - Braoudaki, Maria
JO - Blood cancer journal
PY - 2021
VL - 13
TODO - 21
SP - null
PB - MDPI
SN - null
TODO - 10.3390/cancers13215491
TODO - methylation; childhood CNS tumors; miRNA; mRNA; microarray
TODO - Simple Summary: Epigenetic mechanisms, that are modifications of the
genome without the presence of mutations, are known to play a crucial
role in central nervous system (CNS) tumors during childhood. Two
well-known epigenetic regulatory mechanisms include methylation and
miRNA regulatory mechanisms. Therefore, in the present study we have
investigated the presence of methylated genes in childhood CNS tumors,
along with miRNA expression. We have searched for correlations between
gene methylation and miRNA expression. In addition, we have investigated
mRNA expression in order to search for possible miRNA targets. Such
approaches could prove useful for the improvement of CNS tumor
prognosis, as well as for the discovery of new therapeutic
targets.Epigenetic modifications are considered of utmost significance
for tumor ontogenesis and progression. Especially, it has been found
that miRNA expression, as well as DNA methylation plays a significant
role in central nervous system tumors during childhood. A total of 49
resected brain tumors from children were used for further analysis. DNA
methylation was identified with methylation-specific MLPA and, in
particular, for the tumor suppressor genes CASP8, RASSF1, MGMT, MSH6,
GATA5, ATM1, TP53, and CADM1. miRNAs were identified with microarray
screening, as well as selected samples, were tested for their mRNA
expression levels. CASP8, RASSF1 were the most frequently methylated
genes in all tumor samples. Simultaneous methylation of genes manifested
significant results with respect to tumor staging, tumor type, and the
differentiation of tumor and control samples. There was no significant
dependence observed with the methylation of one gene promoter, rather
with the simultaneous presence of all detected methylated genes'
promoters. miRNA expression was found to be correlated to gene
methylation. Epigenetic regulation appears to be of major importance in
tumor progression and pathophysiology, making it an imperative field of
study.
ER -