Department of Orthopaedics, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China.
Department of Orthopaedics, Air Force General Hospital, People's Liberation Army of China, Beijing 100142, China.
Biomed Pharmacother. 2018 Jan;97:911-918. doi: 10.1016/j.biopha.2017.11.014. Epub 2017 Nov 7.
Osteosarcoma (OS) is the most common type of malignant bone tumor in children and adolescents. However, the molecular mechanism underlying OS development is unclear. Here, we investigated the contribution of lncRNA-p21, a novel long non-coding RNA, on OS cell proliferation. Our results demonstrated that the expression of lncRNA-p21 was repressed in OS tissue. Growth curves and the cell colony formation assay showed that lncRNA-p21 significantly inhibited the proliferation of OS cell lines. In addition, the expression of lncRNA-p21 increased the protein levels of proliferation markers, such as Ki-67 and cyclin D1. Subsequently, lncRNA-p21 overexpression up-regulated the protein level of phosphatase and tensin homolog deleted on chromosome ten (PTEN), a well-known inhibitor of AKT signaling. Moreover, our gain and loss function assay showed that the promotion of PTEN by lncRNA-p21 was mediated by miR-130b, an oncogene overexpressed in OS tissue. Our findings may provide a novel lncRNA-targeted therapy for patients with OS.
骨肉瘤（OS）是儿童和青少年中最常见的恶性骨肿瘤。然而，OS 发展的分子机制尚不清楚。在这里，我们研究了长链非编码 RNA lncRNA-p21 在 OS 细胞增殖中的作用。我们的结果表明，lncRNA-p21 在 OS 组织中表达受到抑制。生长曲线和细胞集落形成实验表明，lncRNA-p21 显著抑制 OS 细胞系的增殖。此外，lncRNA-p21 的表达增加了增殖标志物如 Ki-67 和细胞周期蛋白 D1 的蛋白水平。随后，lncRNA-p21 的过表达上调了磷酸酶和张力蛋白同源物缺失的染色体 10（PTEN）的蛋白水平，PTEN 是 AKT 信号的已知抑制剂。此外，我们的增益和缺失功能实验表明，lncRNA-p21 通过 miR-130b 促进 PTEN 的表达，miR-130b 是 OS 组织中过表达的致癌基因。我们的研究结果可能为 OS 患者提供一种新的 lncRNA 靶向治疗方法。
