engleski

Epigenomics and Translational Research: Challenges and Perspectives

The development of epigenomics extends our horizons for understanding genetic regulation applicable to cellular growth and differentiation, aging and disease. All these depend on multilayer epigenetic networks, established through DNA methylation, histone modifications, chromatin remodeling and microRNAs. DNA hypermethylation itself has been well-noted in cancer patients, as a molecular biomarker of selected tumor suppressor gene inactivation. The integrated methylation status of multiple genes, “methylation score”, may serve as a potential diagnostic and staging biomarker for some types of cancer (prostate cancer). Re-expressing these genes, by using the DNA demethylating agents 5-azacytidine and 5-aza-2'-deoxycytidine, has been shown to be very successful in treating Myelodysplastic Syndrome. Through epigenome networking, hypermethlyated promoters are associated with transcriptional repressor methyl-CpG-binding domain proteins, which serve as cross-talk-linkers to histone molecules and the loss of their active marks (acetylation of histones H3 and H4, trymethylation of histone H3-K4). Currently, the development of histone deacetylase (HDAC) inhibitors opens up a new area of epigenetic cancer therapy. Although the HDAC inhibitors developed to date still do not have the highest level of specificity, they have been shown to be promising anti-cancer agents, as demonstrated in phase I clinical trials. Due to the complexity of the epi-network, much effort needs to be devoted to understanding the basic epigenomic processes. Indeed, integrated, translational research in the field of epigenomics is imperative, not only for therapeutic purposes, but also for potential chemopreventive action.

epigenomics; DNA methylation; epigenomic drugs

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