Epigenetics, Nervous System Tumors, and Cancer Stem Cells

Abstract

Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors.

Histone Deacetylase Inhibitors In The Treatment Of Cancer: Overview And Perspectives

“…Epigenetic deregulation applied to CSCs is a fascinating emerging hypothesis. Early strong evidence on nervous system tumors support a possible approach of epigenetic strategy in the elimination of CSCs [132,133].…”

Effects of prenatal Poly I:C exposure on global histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity in the mouse brain

“…In view of prenatal infection, hypoacetylation of histones H3 and H4 has been observed in the cortex of juvenile offspring prenatally exposed to Poly I:C [ 21 ]. Moreover, HDAC inhibitors are known to impact upon the transcriptional regulation of cytokines, immunologic signaling pathways and the inflammatory response [ 22 ]. To date, the epigenetic effects of prenatal maternal Poly I:C exposure at GD 17-which, as stated above, links more closely to the development of a depressive-like phenotype- have not yet been studied.…”

Developmental and psychoneuroimmunological mechanisms in depression

“…In view of prenatal infection, hypoacetylation of histones H3 and H4 has been observed in the cortex of juvenile offspring prenatally exposed to Poly I:C (Tang, Jia et al 2013). Moreover, HDAC inhibitors are known to impact upon the transcriptional regulation of cytokines, immunologic signaling pathways and the inflammatory response (Qureshi and Mehler 2011). To date, the epigenetic effects of prenatal maternal Poly I:C exposure at GD 17 which, as stated above, links more closely to the development of a depressive-like phenotype have not yet been studied.…”

“…However, as a consequence of their low efficacy in some patients(Nelson 1998, Fournier, DeRubeis et al 2010, new strategies have been investigated, such as HDAC inhibitors. HDAC inhibitors are involved in transcriptional regulation of cytokines, in immunologic signaling pathways, and inflammatory responses (see review byQureshi and Mehler 2011). On the one hand, the commonly used HDAC inhibitor valproic acid (VPA), is found to dedifferentiate committed oligodendrocytes precursors to multipotent neural progenitors, thus inducing neuronal differentiation(Liu, Han et al 2007).…”