Department of Radiology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi Province, 710077, China.
Department of Orthopaedics, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi Province, 710077, China.
Biomed Pharmacother. 2019 Jun;114:108798. doi: 10.1016/j.biopha.2019.108798. Epub 2019 Mar 22.
Long non-coding RNAs (lncRNAs) play a key role in regulating tumor growth and metastasis of osteosarcoma (OS). Recent studies have reported that lncRNA small nucleolar RNA host gene 16 (SNHG16) is highly expressed in OS tissues and contributes to the proliferation, migration and invasion of OS cells. However, the molecular mechanism involved in the oncogenic role of SNHG16 in OS remains poorly known. In the current study, we confirmed that SNHG16 expression was markedly up-regulated in OS tissues compared to paracancerous tissues. The elevated level of SNHG16 closely associated with advanced tumor stages, larger tumor size and more distance metastasis. Furthermore, OS patients with high SNHG16 level had a significant poorer overall survival compared to patients with low SNHG16 level. Knockdown of SNHG16 suppressed the proliferation, migration and invasion of U2OS and MG63 cells. Mechanistically, SNHG16 acted as a competing endogenous RNA (ceRNA) by directly interacting with miR-1301 and inversely regulated its abundance in OS cells. Notably, suppression of miR-1301 rescued SNHG16 knockdown attenuated OS cell proliferation, migration and invasion. SNHG16 knockdown reduced the expression of BCL9 protein in OS cells. Accordingly, BCL9 restoration facilitated the proliferation, migration and invasion of OS cells with SNHG16 knockdown. Collectively, these results suggest that SNHG16 is a potential prognostic biomarker for OS patients. SNHG16 promotes BCL9 expression by sponging miR-1301 to facilitate the proliferation, migration and invasion of OS cells.
长链非编码 RNA（lncRNA）在调节骨肉瘤（OS）的肿瘤生长和转移中起着关键作用。最近的研究表明，lncRNA 小核仁 RNA 宿主基因 16（SNHG16）在 OS 组织中高度表达，并促进 OS 细胞的增殖、迁移和侵袭。然而，SNHG16 在 OS 中的致癌作用所涉及的分子机制仍知之甚少。在本研究中，我们证实 SNHG16 的表达在 OS 组织中明显上调，与癌旁组织相比。SNHG16 的升高水平与肿瘤晚期、肿瘤较大和远处转移密切相关。此外，SNHG16 水平较高的 OS 患者的总生存率明显低于 SNHG16 水平较低的患者。SNHG16 的敲低抑制了 U2OS 和 MG63 细胞的增殖、迁移和侵袭。机制上，SNHG16 通过直接与 miR-1301 相互作用作为竞争性内源性 RNA（ceRNA），并反向调节其在 OS 细胞中的丰度。值得注意的是，抑制 miR-1301 挽救了 SNHG16 敲低减弱的 OS 细胞增殖、迁移和侵袭。SNHG16 敲低降低了 OS 细胞中 BCL9 蛋白的表达。相应地，BCL9 的恢复促进了 SNHG16 敲低的 OS 细胞的增殖、迁移和侵袭。总之，这些结果表明 SNHG16 是 OS 患者的潜在预后生物标志物。SNHG16 通过海绵 miR-1301 促进 BCL9 表达，促进 OS 细胞的增殖、迁移和侵袭。
