Non‐coding RNAs are closely associated with tumorigenesis in multiple malignant tumours, including osteosarcoma (OS). Long non‐coding RNA Ewing sarcoma‐associated transcript 1 (EWSAT1) plays a role in metastasis, and actin cytoskeletal changes in OS remain unclear. In the current study, we showed that EWSAT1 expression was up‐regulated in OS and that an elevation in the EWSAT1 expression level was correlated with poor prognosis in patients with OS. Functionally, we showed that knockdown of EWSAT1 suppressed migration and induced actin stress fibre degradation in MNNG/HOS and 143B cells. Moreover, we found that ROCK1 was a key downstream effector in EWSAT1‐mediated cell migration and actin stress fibre changes. Furthermore, we demonstrated that ROCK1 and EWSAT1 shared a similar microRNA response element of microRNA‐24‐3p (miR‐24‐3p). Moreover, we verified that miR‐24‐3p suppressed ROCK1 and its mediated migration and actin stress fibres change by direct targeting. EWSAT1 promoted ROCK1‐mediated migration and actin stress fibre formation through miR‐24‐3p sponging. Lastly, through an in vivo study, we demonstrated that EWSAT1 promoted lung metastasis in OS. According to the above‐mentioned results, we suggest that EWSAT1 acts as an oncogene and that EWSAT1/miR‐24‐3p/ROCK1 axial could be a new target in the treatment of OS.

中文翻译：

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长链非编码 RNA EWSAT1 通过 miR-24-3p 海绵在骨肉瘤中促进转移和肌动蛋白细胞骨架变化

非编码 RNA 与包括骨肉瘤 (OS) 在内的多种恶性肿瘤的肿瘤发生密切相关。长链非编码 RNA Ewing 肉瘤相关转录物 1 (EWSAT1) 在转移中起作用，而 OS 中肌动蛋白细胞骨架的变化仍不清楚。在目前的研究中，我们发现 EWSAT1 表达在 OS 中上调，并且 EWSAT1 表达水平的升高与 OS 患者的不良预后相关。在功能上，我们发现 EWSAT1 的敲低抑制了 MNNG/HOS 和 143B 细胞中的迁移并诱导肌动蛋白应力纤维降解。此外，我们发现 ROCK1 是 EWSAT1 介导的细胞迁移和肌动蛋白应力纤维变化的关键下游效应器。此外，我们证明 ROCK1 和 EWSAT1 具有相似的 microRNA-24-3p (miR-24-3p) 的 microRNA 反应元件。而且，我们验证了 miR-24-3p 抑制 ROCK1 及其介导的迁移和肌动蛋白应力纤维通过直接靶向发生变化。EWSAT1 通过 miR-24-3p 海绵促进 ROCK1 介导的迁移和肌动蛋白应力纤维的形成。最后，通过体内研究，我们证明 EWSAT1 促进了 OS 中的肺转移。根据上述结果，我们建议 EWSAT1 作为癌基因，EWSAT1/miR-24-3p/ROCK1 轴可能是治疗 OS 的新靶点。