长链非编码 RNA GSEC 通过海绵吸附 miR-588/EIF5A2 轴促进骨肉瘤的增殖、迁移和侵袭。

LncRNA GSEC promotes the proliferation, migration and invasion by sponging miR-588/ EIF5A2 axis in osteosarcoma.

机构信息

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, China; Department of Orthopedics, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330008, China; Nanchang Key Laboratory of Orthopaedics, The Third Affiliated Hospital of Nanchang University, Nanchang, China; Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi, 330006, China.

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

Biochem Biophys Res Commun. 2020 Nov 5;532(2):300-307. doi: 10.1016/j.bbrc.2020.08.056. Epub 2020 Aug 29.

DOI:10.1016/j.bbrc.2020.08.056

PMID:32868080

Abstract

BACKGROUND

Long noncoding RNAs (LncRNAs) show dysregulation in a variety of cancers. However, the function and specific mechanism of LncRNA GSEC in the progression of osteosarcoma remain mostly unknown. In this study, we sought to elucidate the role and mechanism of LncRNA GSEC in the occurrence and progression of osteosarcoma.

METHODS

we examined the expression of LncRNA GSEC in osteosarcoma cell lines by quantitative real time PCR. In vitro experiments, including transwell assays, cck8 assays, and flow cytometry analysis have biologically demonstrated the effect of LncRNA GSEC on the proliferation and migration of osteosarcoma cell lines. Furthermore, the regulation of miR-588 by LncRNA GSEC was determined by luciferase reporter assay and quantitative real time PCR. What's more, subcutaneous tumor formation was performed in nude mice to monitor the growth of the tumor in vivo.

RESULTS

We found that the expression of LncRNA GSEC was up-regulated in osteosarcoma cell lines. Overexpression of LncRNA GSEC promoted the proliferating and migratory capacity, and inhibited the apoptosis of osteosarcoma cells. Conversely, knockdown of LncRNA GSEC resulted in the opposite effect. Mechanistically, we identified LncRNA GSEC functioned as the sponge of miR-588, thus inhibiting the miR-588/EIF5A2 signal pathway. In addition, the expression of miR-588 was negatively correlated with LncRNA GSEC, and the effect by silencing or overexpressing LncRNA GSEC could be rescued by the introduction of miR-588 mimics or inhibitors, respectively.

CONCLUSIONS

In summary, this study shows that LncRNA GSEC promotes the proliferation and invasion of OS through the regulation of miR-588/EIF5A2 pathway, which might provide a new strategy for the treatment of osteosarcoma in the future.

摘要

背景

长链非编码 RNA（LncRNAs）在多种癌症中表现出失调。然而，LncRNA GSEC 在骨肉瘤进展中的功能和具体机制在很大程度上仍然未知。在这项研究中，我们试图阐明 LncRNA GSEC 在骨肉瘤发生和进展中的作用和机制。

方法

我们通过实时定量 PCR 检测骨肉瘤细胞系中 LncRNA GSEC 的表达。体外实验，包括 Transwell 测定、CCK8 测定和流式细胞术分析，从生物学上证明了 LncRNA GSEC 对骨肉瘤细胞系增殖和迁移的影响。此外，通过荧光素酶报告基因测定和实时定量 PCR 确定了 LncRNA GSEC 对 miR-588 的调节。更重要的是，在裸鼠中进行皮下肿瘤形成实验以监测肿瘤在体内的生长。

结果

我们发现 LncRNA GSEC 在骨肉瘤细胞系中表达上调。LncRNA GSEC 的过表达促进了骨肉瘤细胞的增殖和迁移能力，并抑制了细胞凋亡。相反，沉默 LncRNA GSEC 则产生相反的效果。机制上，我们确定 LncRNA GSEC 作为 miR-588 的海绵，从而抑制 miR-588/EIF5A2 信号通路。此外，miR-588 的表达与 LncRNA GSEC 呈负相关，沉默或过表达 LncRNA GSEC 的效果可以分别通过引入 miR-588 模拟物或抑制剂来挽救。