Reversing epigenetics: A potential strategy for treating brain tumor

Recent studies have shown that aberrant epigenetic silencing of anti-tumor genes occurs in various cancers in humans. Foltz et al. have reported two novel tumor suppressor genes namely SDC2 and TMTC1 to be silenced in Glioblastoma multiforme (GBM), the most severe type of brain tumor, by an unusual newly found epigenetic mechanism involving methylation of the histone proteins present in their promoters at their specific tails rather than by the usual epigenetic hypermethylation of the promoter sequences. The expression of these genes was restored in brain tumor cells by inhibiting the methylation process, via silencing of DNA methyl transferases (enzymes that bring about the epigenetic methylation and hence the suppression of these genes) using specific siRNA molecules directed against them. The two genes exhibited growth suppressing anti-cancer effects on brain tumor cells in vitro.

The restoration of expression of epigenetically silenced tumor suppressor genes by inhibiting the methylation of the histone tails in brain tumor cells via the use of specific siRNA molecules targeted against DNA methyl transferases, offers a safe and potential therapeutic strategy to treat brain tumor. Also the epigenetic methylation pattern of these specific genes in the glial cells of the brain and their eventual silencing can be used as a marker for early diagnosis of GBM in patients.

REFERENCE:

Foltz, G., Yoon, J. G., Lee, H., Ryken, T. C., Sibenaller, Z., Ehrich, M., et al. (2009). DNA methyltransferase-mediated transcriptional silencing in malignant glioma: a combined whole-genome microarray and promoter array analysis. Oncogene, 28(29), 2667-2677.


Awais Sharjeel Butt
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