Reciprocal relationship between epi-miRNAs and Epigenetic Modifications in cancer

Epigenetic modifiers play important roles in regulation of the cellular transcriptome. Any imbalance in these processes may lead to abnormal transcriptional activity and thus result in disease state. Distortions of the epigenome have been reported in cancer initiation and progression. Epigenetic regulation usually includes DNA methylation and histone modifications. miRNAs, a class of small noncoding RNAs, frequently deregulated in many diseases including cancer. The connection between epigenetics and miRNAs has been supported by a specific subgroup of miRNAs called ‘‘epi-miRNAs’’that can directly and indirectly modulate the activity of the epigenetic machinery. The retrieved studies were searched through the PubMed (MEDLINE), Google Scholar, Scopus, databases. Different studies have been demonstrated that Changes in DNA methylation, altered histone modifications and epi-miRNA expression are functionally associated with cancer initiation and progression. Various aspects of the epigenome have also been investigated as biomarkers for different stages of cancer detection.Oncogenic miRNAs, can all serve as important targets in cancer therapy; knocking down of these miRNAs may stunt the cancer growth. On the other hand, restoring tumor-suppressor miRNAs can also be a powerful approach in treating cancer. The finding that epigenetic drugs 5-Aza-2′-deoxycytidine is able to lead to the up-regulation of miR-127, which can down-regulate BCL6, is especially exciting. Furthermore it demonstrates that epigenetics drugs may exert their antitumor effects on two fronts: they not only turn on have the tumor-suppressor had genes that were aberrantly silenced epigenetically, but they also turned on tumor-suppressor miRNAs that down-regulate target oncogenic mRNAs.

Keywords:

epigenetics: DNA methylation , histone modifications , epi-microRNA