Department of Physiology Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland.
Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Int J Mol Sci. 2021 Jul 27;22(15):8023. doi: 10.3390/ijms22158023.
Rhabdomyosarcoma (RMS) is a malignant soft tissue cancer that develops mostly in children and young adults. With regard to histopathology, four rhabdomyosarcoma types are distinguishable: embryonal, alveolar, pleomorphic and spindle/sclerosing. Currently, increased amounts of evidence indicate that not only gene mutations, but also epigenetic modifications may be involved in the development of RMS. Epigenomic changes regulate the chromatin architecture and affect the interaction between DNA strands, histones and chromatin binding proteins, thus, are able to control gene expression. The main aim of the study was to assess the role of protein arginine methyltransferases (PRMT) in the cellular biology of rhabdomyosarcoma. In the study we used two pan-inhibitors of PRMT, called AMI-1 and SAH, and evaluated their effects on proliferation and apoptosis of RMS cells. We observed that AMI-1 and SAH reduce the invasive phenotype of rhabdomyosarcoma cells by decreasing their proliferation rate, cell viability and ability to form cell colonies. In addition, microarray analysis revealed that these inhibitors attenuate the activity of the PI3K-Akt signaling pathway and affect expression of genes related to it.
横纹肌肉瘤（RMS）是一种主要发生在儿童和年轻人中的恶性软组织癌症。就组织病理学而言，可区分出四种横纹肌肉瘤类型：胚胎性、肺泡性、多形性和梭形/硬化性。目前，越来越多的证据表明，不仅基因突变，而且表观遗传修饰也可能参与 RMS 的发展。表观基因组变化调节染色质结构，并影响 DNA 链、组蛋白和染色质结合蛋白之间的相互作用，从而能够控制基因表达。本研究的主要目的是评估蛋白质精氨酸甲基转移酶（PRMT）在横纹肌肉瘤细胞生物学中的作用。在研究中，我们使用了两种称为 AMI-1 和 SAH 的 PRMT 泛抑制剂，并评估了它们对 RMS 细胞增殖和凋亡的影响。我们观察到，AMI-1 和 SAH 通过降低增殖率、细胞活力和形成细胞集落的能力来降低横纹肌肉瘤细胞的侵袭表型。此外，微阵列分析显示，这些抑制剂减弱了 PI3K-Akt 信号通路的活性，并影响了与之相关的基因的表达。
