Targeting epigenetic regulations in cancer

Abstract

Epigenetic regulation of gene expression is a dynamic and reversible process with DNA methylation, histone modifications, and chromatin remodeling. Recently, groundbreaking studies have demonstrated the importance of DNA and chromatin regulatory proteins from different aspects, including stem cell, development, and tumor genesis. Abnormal epigenetic regulation is frequently associated with diseases and drugs targeting DNA methylation and histone acetylation have been approved for cancer therapy. Although the network of epigenetic regulation is more complex than people expect, new potential druggable chromatin-associated proteins are being discovered and tested for clinical application. Here we review the key proteins that mediate epigenetic regulations through DNA methylation, the acetylation and methylation of histones, and the reader proteins that bind to modified histones. We also discuss cancer associations and recent progress of pharmacological development of these proteins.

Emerging Roles of Epigenetic Regulator Sin3 in Cancer

“…Epigenome, in broader terms, refers to reversible and dynamic regulation of gene expression by chromatin-associated factors, independent of primary DNA sequence. These epigenetic factors include proteins that are members of large multiprotein complexes and act as readers or modifiers of numerous epigenetic regulations including DNA methylation, histone modifications, chromatin remodeling, and RNA interference (RNAi) (Ning, Li, Zhao, & Wang, 2015). Recently, intriguing evidence implicate genetic mutations and/or aberrant recruitment of epigenetic regulators in tumorigenesis (reviewed in You & Jones, 2012).…”

Phosphorylation of LSD1 by PLK1 promotes its chromatin release during mitosis

“…Fine control of the balance of histone methyltransferase/demethylase activities is essential for cell cycle progression and maintenance of genome integrity [18]. Tipping the balance toward either direction could be detrimental.…”

Modulation of the Endothelin System in Colorectal Cancer Liver Metastasis: Influence of Epigenetic Mechanisms?

“…However, the decreased expression of Edn1 was probably caused by a different mechanism of action, which might have been activated by the increased levels of EdnrB and/or Ece1 mRNA, as suggested by the short but discernable time lag between the increased expression of EdnrB and/or Ece1 mRNA and the decreased expression of Edn1. To better understand this situation, we set up experiments in which human and rat CRC cells were treated with the demethylating agent DAC, which acts through inhibition of DNA methyltransferase enzymes DNMT1 and DNMT3 (Ning et al, 2016).…”