Department of Orthopaedics, Jiading District Anting Hospital of Shanghai, Shanghai, 201805, China.
Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Hum Cell. 2022 Jan;35(1):250-259. doi: 10.1007/s13577-021-00615-y. Epub 2021 Oct 9.
Osteosarcoma (OS) is a common, highly malignant bone tumor. Tripartite motif-containing protein 59 (TRIM59) has been identified as a potential oncogenic protein involved in the initiation and progression of various human carcinomas. Nonetheless, the possible roles and molecular mechanisms of action of TRIM59 in OS remain unclear. In this study, we found that TRIM59 expression levels were frequently upregulated in OS tissues and cell lines. TRIM59 knockdown significantly suppressed the proliferation, migration, and invasion of OS cells and promoted OS cell apoptosis, whereas TRIM59 overexpression had the opposite effects. In vivo experiments demonstrated that TRIM59 knockdown suppressed OS tumor growth and metastasis in vivo. Furthermore, we found that TRIM59 directly interacted with phospho-STAT3 in OS cells. The downregulation of STAT3 levels attenuated TRIM59-induced cell proliferation and invasion. Taken together, our results indicate that TRIM59 promoted OS progression via STAT3 activation. Therefore, our study may provide a novel therapeutic target for OS.
骨肉瘤（OS）是一种常见的高度恶性骨肿瘤。三结构域蛋白 59（TRIM59）已被鉴定为一种潜在的致癌蛋白，参与各种人类癌的发生和进展。然而，TRIM59 在 OS 中的可能作用和分子机制尚不清楚。在本研究中，我们发现 TRIM59 表达水平在 OS 组织和细胞系中经常上调。TRIM59 敲低显著抑制 OS 细胞的增殖、迁移和侵袭，并促进 OS 细胞凋亡，而 TRIM59 过表达则有相反的效果。体内实验表明，TRIM59 敲低抑制了体内 OS 肿瘤的生长和转移。此外，我们发现 TRIM59 直接与 OS 细胞中的磷酸化 STAT3 相互作用。STAT3 水平的下调减弱了 TRIM59 诱导的细胞增殖和侵袭。总之，我们的研究结果表明，TRIM59 通过激活 STAT3 促进 OS 的进展。因此，我们的研究可能为 OS 提供了一个新的治疗靶点。
