Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100, Sassari, Italy.
Kitos Biotech Srls, Tramariglio, Alghero, SS, Italy.
Clin Epigenetics. 2021 Aug 9;13(1):156. doi: 10.1186/s13148-021-01147-w.
Skeletal muscle formation represents a complex of highly organized and specialized systems that are still not fully understood. Epigenetic systems underline embryonic development, maintenance of stemness, and progression of differentiation. Polycomb group proteins play the role of gene silencing of stemness markers that regulate muscle differentiation. Enhancer of Zeste EZH2 is the catalytic subunit of the complex that is able to trimethylate lysine 27 of histone H3 and induce silencing of the involved genes. In embryonal Rhabdomyosarcoma and several other tumors, EZH2 is often deregulated and, in some cases, is associated with tumor malignancy. This review explores the molecular processes underlying the failure of muscle differentiation with a focus on the PRC2 complex. These considerations could open new studies aimed at the development of new cutting-edge therapeutic strategies in the onset of Rhabdomyosarcoma.
骨骼肌的形成代表了一个高度组织化和专业化的系统复合体，这些系统仍未被完全理解。表观遗传系统是胚胎发育、干细胞维持和分化进展的基础。多梳蛋白组蛋白抑制复合物（PcG）发挥着抑制干细胞标志物基因表达的作用，这些标志物调控肌肉的分化。EZH2 是 PcG 复合物的催化亚基，能够使组蛋白 H3 赖氨酸 27 发生三甲基化，并诱导相关基因沉默。在胚胎性横纹肌肉瘤和其他几种肿瘤中，EZH2 常常失调，在某些情况下与肿瘤的恶性程度有关。本综述探讨了肌肉分化失败的分子过程，重点是 PRC2 复合物。这些考虑因素可能为横纹肌肉瘤发病机制中开发新的前沿治疗策略开辟新的研究途径。
