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长链非编码 RNA MEG3 通过海绵吸附 miR-127 抑制骨肉瘤细胞的活力、迁移和侵袭并促进细胞凋亡。

Knockdown of lncRNA MEG3 inhibits viability, migration, and invasion and promotes apoptosis by sponging miR-127 in osteosarcoma cell.

机构信息

Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, China.

出版信息

J Cell Biochem. 2018 Jan;119(1):669-679. doi: 10.1002/jcb.26230. Epub 2017 Jul 31.

DOI:10.1002/jcb.26230
PMID:28636101
Abstract

Osteosarcoma (OS) is one of the most common bone malignancies and occurs almost exclusively in children and adolescents. This study aimed to explore the role of lncRNA maternally expressed gene 3 (MEG3) in OS cells growth and metastasis, and to uncover the possible underlying mechanism. In this study, the expressions of MEG3 in five OS cell lines (MG63, OS-732, SaOS, G292, and 143B) and in a human osteoblast cell line hFOB1.19 were measured by qRT-PCR analysis. The expressions of MEG3, miR-127, and ZEB1 in OS-732 cells were overexpressed or suppressed by transfection. Cell viability, migration, invasion, and apoptosis were then assessed. The results showed that MEG3 was highly expressed in OS cell lines when compared to hFOB1.19 cell. MEG3 silence significantly suppressed OS-732 cells growth and metastasis, as evidenced by the decreases in cell viability, migration, invasion, and increase in apoptotic cell rate. MEG3 acted as an endogenous sponge by binding to miR-127. More interestingly, MEG3 silence could not suppress OS-732 cells growth and metastasis when miR-127 was knocked down. ZEB1 was a target gene of miR-127, and miR-127 overexpression-induced impairments in cell growth and metastasis were attenuated when ZEB1 was overexpressed. Moreover,miR-127 suppression activated JNK and Wnt signaling pathways, while these activations were recovered by ZEB1 silence. To conclude, our findings suggest that lncRNA MEG3 promoted OS cells growth and metastasis in vitro through sponging miR-127. This study provides the evidence that MEG3 may be a potential therapeutic target for OS.

摘要

骨肉瘤(OS)是最常见的骨恶性肿瘤之一,几乎仅发生于儿童和青少年。本研究旨在探讨长链非编码 RNA 母源表达基因 3(MEG3)在 OS 细胞生长和转移中的作用,并揭示其潜在的机制。在本研究中,通过 qRT-PCR 分析测定了 MEG3 在五株 OS 细胞系(MG63、OS-732、SaOS、G292 和 143B)和人成骨细胞系 hFOB1.19 中的表达。通过转染过表达或抑制 OS-732 细胞中的 MEG3、miR-127 和 ZEB1 的表达。然后评估细胞活力、迁移、侵袭和凋亡。结果表明,与 hFOB1.19 细胞相比,MEG3 在 OS 细胞系中高表达。MEG3 沉默显著抑制 OS-732 细胞的生长和转移,表现在细胞活力、迁移、侵袭减少和凋亡细胞率增加。MEG3 通过与 miR-127 结合作为内源性海绵。更有趣的是,当 miR-127 被敲低时,MEG3 沉默不能抑制 OS-732 细胞的生长和转移。ZEB1 是 miR-127 的靶基因,当过表达 ZEB1 时,miR-127 过表达诱导的细胞生长和转移损伤减弱。此外,miR-127 抑制激活 JNK 和 Wnt 信号通路,而这些激活通过 ZEB1 沉默得到恢复。总之,我们的研究结果表明,lncRNA MEG3 通过海绵吸附 miR-127 促进 OS 细胞体外生长和转移。本研究为 MEG3 可能成为 OS 的潜在治疗靶点提供了证据。

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