18 R. Macri, M. Costilla, A. Klecha et al.
accelerates the MYC oncogene-mediated lymphomagenesis. Moreover,
patients with diffuse large B-cell lymphomas (DLBCLs) and PRDM11
deficients have a lower survival. Also, PRDM11 is a novel tumor suppressor
that associates with transcriptional start sites of oncogenes such as FOS and
JUN, downregulating their expression.
Colorectal cancer (CRC) remains to be one of the most common causes of
cancer-related death 13 . Aberrant methylation of DNA is an alteration
epigenomic prevalent in the CRC, in combination with the BRAF mutation
13 . PRC proteins mediate trimethylation of the lysines 9 and 27 of histone
H3 (H3K9me3 y H3K27me3) silencing a TSG specific group in human
cancers. It has been found in the CRC that folate deficiency induces the
hypermethylation of specific genes and global hypomethylation of genome
14 .
Prostata cancer (CaP) is one of the most common human cancers
generated by genetic and epigenetic mechanisms. Retinoic Acid Receptor β
(RARβ) is a TSG frequently silenced in CaP by promoter methylation. Also,
DNA methylation levels are positively correlated with trimethylation of the
lysine 27 of histone H3 mediated by PRC proteins 15 . In addition,
deregulation of miRNA expression can have a critical role in prostate
carcinogenesis. It has been shown in prostate cancer that miRNA- 205
transcription is commonly repressed by hypermethylation. The downregulation
of the expression of miRNA 205 increases the MED1 expression contributing
to tumor progression. So, miRNA-205 is an epigenetically regulated tumor
suppressor that could be a potential biomarker in prostate cancer 16 .
EPIGENETIC THERAPY
Several epigenetic alterations can produce the silencing of TSG or inhibit
the function of the miRNAs. These epigenetic changes can be reversed by
treatment with DNMT and HDAC inhibitors. So, DNMT or HDAC inhibitors
can produce the hypomethylation at the promoters of genes, inducing the
expression of TSG, cell differentiation or death by apoptosis.
Many drugs commonly used for the treatment of cancer have high
toxicity, undesirable side effects and often generate resistance, an example of
this is the use of doxorubicin or daunorubicin for the treatment of breast
cancer. Also, there is evidence that epigenetic alterations might be responsible