Oncol Res. 2017 Sep 21;25(8):1297-1304. doi: 10.3727/096504017X14873430389189. Epub 2017 Feb 28.
Spinal osteosarcoma (OS) is a malignant tumor that has a poor outcome. MicroRNA-520b (miR-520b) acts as a cancer suppressor in various types of cancer. Because of the limited amount of literature on OS, we aimed to identify the role of miR-520b in OS. The miR-520b level in clinical spinal OS tissues and adjacent nontumor tissues as well as in cell lines was assessed. The effect of miR-520b on cell proliferation, migration, invasion, and frizzled-8 (FZD8) degradation were all evaluated. Alterations of key proteins involved in the Wnt/β-catenin pathway were assessed by Western blot analysis. In the present study, miR-520b was downregulated in human spinal OS tissues and OS cell lines (p < 0.01 or p < 0.001). Overexpression of miR-520b inhibited cell proliferation (p < 0.01 or p < 0.001), migration (p < 0.01), and invasion (p < 0.01). FZD8 expression was negatively regulated by infection with a lentivirus vector carrying an miR-520b precursor in dose- and time-dependent manners. In OS tissues, miR-520b was inversely correlated with FZD8 expression. FZD8 was upregulated in human spinal OS tissues and cell lines. Finally, miR-520b inactivated the Wnt/β-catenin pathway through downregulation of FZD8. miR-520b inhibited cell proliferation, migration, and invasion through inactivating the Wnt/β-catenin pathway by downregulation of FZD8, providing a novel therapeutic target for spinal OS.
脊柱骨肉瘤(OS)是一种预后不良的恶性肿瘤。MicroRNA-520b(miR-520b)在多种类型的癌症中充当肿瘤抑制因子。由于关于 OS 的文献数量有限,我们旨在确定 miR-520b 在 OS 中的作用。评估了临床脊柱 OS 组织和相邻非肿瘤组织以及细胞系中 miR-520b 的水平。评估了 miR-520b 对细胞增殖、迁移、侵袭和卷曲受体 8(FZD8)降解的影响。通过 Western blot 分析评估了参与 Wnt/β-catenin 通路的关键蛋白的变化。在本研究中,miR-520b 在人脊柱 OS 组织和 OS 细胞系中下调(p < 0.01 或 p < 0.001)。miR-520b 的过表达抑制细胞增殖(p < 0.01 或 p < 0.001)、迁移(p < 0.01)和侵袭(p < 0.01)。FZD8 的表达受携带 miR-520b 前体的慢病毒载体感染以剂量和时间依赖性方式负调控。在 OS 组织中,miR-520b 与 FZD8 的表达呈负相关。FZD8 在人脊柱 OS 组织和细胞系中上调。最后,miR-520b 通过下调 FZD8 使 Wnt/β-catenin 通路失活。miR-520b 通过下调 FZD8 使 Wnt/β-catenin 通路失活,从而抑制细胞增殖、迁移和侵袭,为脊柱 OS 提供了新的治疗靶点。