Table_1_Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma.XLSX

Fusion-negative rhabdomyosarcoma (FN-RMS) is the most common soft tissue sarcoma of childhood arising from undifferentiated skeletal muscle cells from uncertain origin. Currently used therapies are poorly tumor-specific and fail to tackle the molecular machinery underlying the tumorigenicity and uncontrolled proliferation of FN-RMS. We and other groups recently found that microRNAs (miRNA) network contributes to myogenic epigenetic memory and can influence pluripotent stem cell commitments. Here, we used the previously identified promyogenic miRNAs and tailored it to the murine FN-RMS. Subsequently, we addressed the effects of miRNAs in vivo by performing syngeneic transplant of pre-treated FN-RMS cell line in C57Bl/6 mice. miRNA pre-treatment affects murine FN-RMS cell proliferation in vivo as showed by bioluminescence imaging analysis, resulting in better muscle performances as highlighted by treadmill exhaustion tests. In conclusion, in our study we identified a novel miRNA combination tackling the anti-myogenic features of FN-RMS by reducing proliferation and described novel antitumorigenic therapeutic targets that can be further explored for future pre-clinical applications.

融合阴性横纹肌肉瘤（FN-RMS）是儿童最常见的软组织肉瘤，起源于起源不明的未分化骨骼肌细胞。目前采用的疗法肿瘤特异性较差，未能解决FN-RMS肿瘤发生性和无控制增殖背后的分子机制。我们及其他研究团队近期发现，microRNA（miRNA）网络参与肌原性表观遗传记忆，并能影响多能干细胞的分化承诺。在本研究中，我们应用先前鉴定出的促肌原性miRNA，并针对小鼠FN-RMS进行定制。随后，通过在C57Bl/6小鼠中进行预先处理的FN-RMS细胞系的同基因移植，我们研究了miRNA在体内的作用。miRNA预处理通过生物发光成像分析显示，影响了小鼠FN-RMS细胞在体内的增殖，并通过跑步机耐力测试突显了更好的肌肉表现。总之，在我们的研究中，我们识别了一种新型miRNA组合，通过减少增殖来对抗FN-RMS的肌原性特征，并描述了新的抗肿瘤治疗靶点，这些靶点可进一步探索，以用于未来的临床前应用。