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lncRNA 核富集丰富转录本 1 通过靶向 miR-186-5p/HIF-1α 促进骨肉瘤细胞增殖和侵袭。

lncRNA nuclear-enriched abundant transcript 1 promotes cell proliferation and invasion by targeting miR-186-5p/HIF-1α in osteosarcoma.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):6502-6514. doi: 10.1002/jcb.27941. Epub 2018 Nov 28.

Abstract

Increasing evidence shows that the long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) plays important roles in tumor progression. However, the function and the underlying mechanism of NEAT1 in osteosarcoma (OS) remain unclear. In the present study, we found that NEAT1 expression was significantly upregulated in OS tissues and cell lines. High NEAT1 expression was closely associated with advanced clinicopathologic features and poor overall survival of patients with OS. Using in vitro function assay, we found that NEAT1 could promote the proliferation, invasion, and epithelial-mesenchymal transition (EMT) process of OS cells. NEAT1 could also promote OS cell growth in vivo. In addition, our studies showed that miR-186-5p was a downstream target of NEAT1 in OS. Functionally, miR-186-5p suppressed the proliferation, invasion, and EMT process of OS cells. Furthermore, our data revealed that HIF-1α was a downstream target of miR-186-5p and that NEAT1 could exert its tumor oncogenic roles on OS cells via the miR-186-5p/HIF-1α axis. Taking our results together, we elucidated that the NEAT1/miR-186-5p/HIF-1α axis might be a therapeutic approach for the treatment of OS.

摘要

越来越多的证据表明,长链非编码 RNA 核丰富丰富转录物 1(NEAT1)在肿瘤进展中发挥重要作用。然而,NEAT1 在骨肉瘤(OS)中的功能和潜在机制仍不清楚。在本研究中,我们发现 NEAT1 表达在 OS 组织和细胞系中显著上调。高 NEAT1 表达与 OS 患者晚期临床病理特征和总体生存率差密切相关。通过体外功能测定,我们发现 NEAT1 可促进 OS 细胞的增殖、侵袭和上皮-间充质转化(EMT)过程。NEAT1 还可以促进 OS 细胞在体内的生长。此外,我们的研究表明,miR-186-5p 是 OS 中 NEAT1 的下游靶标。功能上,miR-186-5p 抑制 OS 细胞的增殖、侵袭和 EMT 过程。此外,我们的数据显示 HIF-1α 是 miR-186-5p 的下游靶标,NEAT1 可以通过 miR-186-5p/HIF-1α 轴发挥其在 OS 细胞中的肿瘤致癌作用。综合我们的结果,我们阐明了 NEAT1/miR-186-5p/HIF-1α 轴可能是治疗 OS 的一种治疗方法。

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