Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Cell Prolif. 2018 Dec;51(6):e12515. doi: 10.1111/cpr.12515. Epub 2018 Aug 28.
Accumulating data show that dysregulation of long noncoding RNAs (lncRNAs) acts a critical role in a variety of malignancies. Among these lncRNAs, small nucleolar RNA host genes (SNHGs) are associated with tumour growth and progression. But, the molecular mechanisms by which SNHG4 contributes to osteosarcoma remain undocumented.
The association between lncRNA SNHG4 expression and clinicopathologic characteristics and prognosis in patients with osteosarcoma was analysed by TCGA RNA-sequencing data. Cell viability and colony formation abilities were respectively assessed by MTT and colony formation assays. LncRNA SNHG4-specific binding with miR-224-3p was verified by bioinformatic analysis, luciferase gene report, and RNA immunoprecipitation assays. Regulation relationship between SNHG4 and miR-224-3p expression was further evaluated by the rescue experiments.
The expression level of lncRNA SNHG4 was significantly elevated in osteosarcoma samples and cell lines as compared with the adjacent normal tissues, and SNHG4 high expression was associated with tumour size (TS) and poor prognosis in patients with osteosarcoma. Knockdown of SNHG4 suppressed cell viability and invasive potential, whereas ectopic SNHG4 expression displayed the opposite effects. Moreover, we found that lncRNA SNHG4 acted as a sponge of miR-224-3p, and miR-224-3p mimic reversed SNHG4 induced tumour-promoting effects in osteosarcoma cells. The expression of miR-224-3p depicted a negative correlation with SNHG4 in osteosarcoma samples and miR-224-3p low expression was associated with TS and poor survival in patients with osteosarcoma.
Our findings demonstrated that LncRNA SNHG4 promoted tumour growth by sponging miR-224-3p and represented a poor prognostic factor in patients with osteosarcoma.
越来越多的数据表明，长链非编码 RNA（lncRNA）的失调在多种恶性肿瘤中起着关键作用。在这些 lncRNA 中，核仁小分子 RNA 宿主基因（SNHGs）与肿瘤的生长和进展有关。但是，SNHG4 促进骨肉瘤的分子机制尚未被记录。
通过 TCGA RNA 测序数据分析骨肉瘤患者 lncRNA SNHG4 表达与临床病理特征和预后的关系。通过 MTT 和集落形成测定分别评估细胞活力和集落形成能力。通过生物信息学分析、荧光素酶基因报告和 RNA 免疫沉淀测定验证 lncRNA SNHG4 与 miR-224-3p 的特异性结合。通过挽救实验进一步评估 SNHG4 和 miR-224-3p 表达之间的调节关系。
与相邻正常组织相比，骨肉瘤样本和细胞系中 lncRNA SNHG4 的表达水平显著升高，SNHG4 高表达与骨肉瘤患者的肿瘤大小（TS）和预后不良相关。SNHG4 敲低抑制细胞活力和侵袭潜能，而外源性 SNHG4 表达则表现出相反的效果。此外，我们发现 lncRNA SNHG4 作为 miR-224-3p 的海绵，miR-224-3p 模拟物逆转了 SNHG4 在骨肉瘤细胞中促进肿瘤的作用。骨肉瘤样本中 miR-224-3p 的表达与 SNHG4 呈负相关，miR-224-3p 低表达与骨肉瘤患者的 TS 和生存不良相关。
我们的研究结果表明，LncRNA SNHG4 通过海绵 miR-224-3p 促进肿瘤生长，并且在骨肉瘤患者中是一个不良的预后因素。
