Hao Haihu, Wang Li, Liu Qiang, Wu Dou, Xing Hao
Department of Orthopedics, Shanxi Academy of Medical Sciences & Shanxi Bethune Hospital Taiyuan 030032, China.
Department of Pathology, Shanxi Medical University Taiyuan 030001, China.
Am J Transl Res. 2020 Jul 15;12(7):3476-3488. eCollection 2020.
Osteosarcoma (OS) is the most leading primary malignant tumor of the bone in adolescents and young adults worldwide. Increasing data have suggested that long non-coding RNA (lncRNA) small nucleolar RNA host gene 8 (SNHG8) plays a key role in the progression of various types of human malignancy. However, the roles and potential mechanisms of SNHG8 in OS remain unclear. In this study, we found that SNHG8 levels were obviously upregulated in OS tissues and cell lines. High expression of SNHG8 was significantly correlated with increased tumor size and advanced Enneking stage, and predicted a poor prognosis of OS patients. Functional assays revealed that SNHG8 knockdown inhibited OS cell growth and migration , and restrained tumor growth of OS in nude mice . Mechanistically, SNHG8 functioned as a competing endogenous RNA (ceRNA) of miR-876-5p in OS cells. Notably, knockdown of miR-876-5p reversed the inhibitory effects of SNHG8 inhibition on OS cell proliferation and migration. In conclusion, our study suggested that SNHG8 stimulates cell growth and migration of OS cells by functioning as a ceRNA of miR-876-5p, indicating SNHG8 may be served as a novel prognostic biomarker and therapeutic target for the treatment of OS.
骨肉瘤(OS)是全球青少年和年轻成年人中最主要的原发性骨恶性肿瘤。越来越多的数据表明,长链非编码RNA(lncRNA)小核仁RNA宿主基因8(SNHG8)在各种类型的人类恶性肿瘤进展中起关键作用。然而,SNHG8在骨肉瘤中的作用和潜在机制仍不清楚。在本研究中,我们发现骨肉瘤组织和细胞系中SNHG8水平明显上调。SNHG8的高表达与肿瘤大小增加和Enneking分期进展显著相关,并预示着骨肉瘤患者预后不良。功能试验表明,敲低SNHG8可抑制骨肉瘤细胞生长和迁移,并抑制裸鼠骨肉瘤的肿瘤生长机制上,SNHG8在骨肉瘤细胞中作为miR-876-5p的竞争性内源性RNA(ceRNA)发挥作用。值得注意的是,敲低miR-876-5p可逆转SNHG8抑制对骨肉瘤细胞增殖和迁移的抑制作用。总之,我们的研究表明,SNHG8通过作为miR-876-5p的ceRNA刺激骨肉瘤细胞的生长和迁移,表明SNHG8可能作为一种新的预后生物标志物和骨肉瘤治疗的靶点。