Osteosarcoma is a common malignancy of the bone tissue. The rapid growth exhibited by this cancer is a primary challenge in its treatment. In many types of cancers, FAT10, a ubiquitin-like protein, is involved in several biological activities, especially cell proliferation. Herein, we demonstrate that FAT10 plays a vital role in tumorigenesis and is overexpressed in tumor tissues compared to its expression in adjacent normal tissues. Functional assays revealed that knockdown of FAT10 expression significantly repressed the proliferation of osteosarcoma in vitro and in vivo. Furthermore, our results indicate that FAT10 exhibits oncogenic functions by regulating the level of YAP1, a key protein of the Hippo/YAP signaling pathway, and a significant positive correlation exists between the levels of FAT10 and YAP1. Further analysis showed that FAT10-induced growth of osteosarcoma cells is dependent on YAP1. Mechanistically, FAT10 stabilizes YAP1 expression by regulating its ubiquitination and degradation. Taken together, our results link the two drivers of cell growth in osteosarcoma and reveal a novel pathway for FAT10 regulation. We provide new evidence for the biological and clinical significance of FAT10 as a potential biomarker for osteosarcoma.

中文翻译：

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泛素样蛋白FAT10通过修饰YAP1的泛素化和降解来促进骨肉瘤的生长。

骨肉瘤是骨组织的常见恶性肿瘤。这种癌症表现出的快速生长是其治疗中的主要挑战。在许多类型的癌症中，类似于泛素的蛋白质FAT10都参与了多种生物学活动，尤其是细胞增殖。在本文中，我们证明FAT10在肿瘤发生中起着至关重要的作用，与其在邻近正常组织中的表达相比，在肿瘤组织中过表达。功能测定表明，FAT10表达的敲低显着抑制了体外和体内骨肉瘤的增殖。此外，我们的结果表明，FAT10通过调节Hippo / YAP信号通路的关键蛋白YAP1的水平表现出致癌功能，并且FAT10和YAP1的水平之间存在显着的正相关。进一步的分析表明，FAT10诱导的骨肉瘤细胞生长依赖于YAP1。从机制上讲，FAT10通过调节其泛素化和降解来稳定YAP1表达。综上所述，我们的结果将骨肉瘤中细胞生长的两个驱动因素联系在一起，揭示了FAT10调控的新途径。我们为FAT10作为骨肉瘤的潜在生物标志物的生物学和临床意义提供了新的证据。