Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs’ roles in osteosarcoma metastasis are still unknown. Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves. Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients’ prognosis. The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.

中文翻译：

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长链非编码 RNA 相关竞争性内源性 RNA 网络用于骨肉瘤转移的开发和分析

骨肉瘤是原发性骨恶性肿瘤，常发生转移。越来越多的证据表明，非编码 RNA (ncRNA) 与骨肉瘤的进展有关。然而，ncRNAs在骨肉瘤转移中的作用仍然未知。从基因表达综合 (GEO) 数据库中鉴定出差异表达 (DE) RNA。DE 信使 RNA (DEmRNAs) 的蛋白质-蛋白质相互作用 (PPI) 是通过 STRING 数据库建立的。通过 miRDB、Targetscan 和 Genecode 数据库预测 microRNA (miRNA) 的目标 mRNA 和长 ncRNA (lncRNA)，然后与先前获得的 DERNA 进行交叉检查，以构建竞争性内源 RNA (ceRNA) 网络。所有网络均通过 Cytoscape 进行可视化，并通过 Cytoscape 插件 Cytohubba 筛选出中枢 RNA。通过 DAVID 和 MirPath 数据库进行基因功能和通路分析。通过 Kaplan-Meier (KM) 生存曲线获得集线器 RNA 的生存分析。筛选出564个DEmRNAs、16个DElncRNAs和22个DEmiRNAs。GO 功能和 KEGG 通路分析表明，DERNA 与肿瘤转移显着相关。构建了包括 6 个 lncRNA、55 个 mRNA 和 20 个 miRNA 的 ceRNA 网络，并获得了前 10 个中枢 RNA。最重要的是，PI3K/AKT 信号通路被确定为最重要的骨肉瘤转移相关通路，并构建了其枢纽 ceRNA 模块。生存分析表明，hub ceRNA模块中的RNA与骨肉瘤患者的预后密切相关。目前的研究为骨肉瘤转移提供了新的视角。