Targeting the epigenome of cancer stem cells in pediatric nervous system tumors

• Published in: Molecular and cellular biochemistry 2023-10, Vol.478 (10), p.2241-2255
• Main Authors: Freire, Natália Hogetop, Jaeger, Mariane da Cunha, de Farias, Caroline Brunetto, Nör, Carolina, Souza, Barbara Kunzler, Gregianin, Lauro, Brunetto, André Tesainer, Roesler, Rafael
• Format: Article
• Language: English
• Subjects: Amino acids; Biochemistry; Biomedical and Life Sciences; Brain cancer; Brain tumors; Cancer; Cancer Research; Cardiology; Cell differentiation; Cell self-renewal; Chromatin; Chromatin remodeling; Development and progression; Developmental stages; Differentiation; DNA methylation; Drug development; Epigenetic inheritance; Epigenetics; Gene regulation; Genes; Glial fibrillary acidic protein; Glioma; Gliomas; Histones; Life Sciences; Medical Biochemistry; Medulloblastoma; Methylation; MicroRNA; miRNA; Modulators; Nervous system; Nervous system tumors; Neural stem cells; Neuroblastoma; Neuromodulation; Neurophysiology; Pediatrics; Pluripotency; Progenitor cells; Ribonucleic acid; RNA; S100b protein; Stem cell research; Stem cells; Tumors; Vorinostat
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-022-04655-2

Medulloblastoma, neuroblastoma, and pediatric glioma account for almost 30% of all cases of pediatric cancers. Recent evidence indicates that pediatric nervous system tumors originate from stem or progenitor cells and present a subpopulation of cells with highly tumorigenic and stem cell-like features. These cancer stem cells play a role in initiation, progression, and resistance to treatment of pediatric nervous system tumors. Histone modification, DNA methylation, chromatin remodeling, and microRNA regulation display a range of regulatory activities involved in cancer origin and progression, and cellular identity, especially those associated with stem cell features, such as self-renewal and pluripotent differentiation potential. Here, we review the contribution of different epigenetic mechanisms in pediatric nervous system tumor cancer stem cells. The choice between a differentiated and undifferentiated state can be modulated by alterations in the epigenome through the regulation of stemness genes such as CD133, SOX2, and BMI1 and the activation neuronal of differentiation markers, RBFOX3, GFAP, and S100B. Additionally, we highlighted the stage of development of epigenetic drugs and the clinical benefits and efficacy of epigenetic modulators in pediatric nervous system tumors.