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SP1 介导的长链非编码 RNA ILF3-AS1 的上调作为 ceRNA 通过调节 SOX5 促进骨肉瘤的进展。

SP1-mediated upregulation of lncRNA ILF3-AS1 functions a ceRNA for miR-212 to contribute to osteosarcoma progression via modulation of SOX5.

机构信息

Department of Orthopedics, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, 223300, China.

Department of Orthopedics, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, 223300, China.

出版信息

Biochem Biophys Res Commun. 2019 Apr 9;511(3):510-517. doi: 10.1016/j.bbrc.2019.02.110. Epub 2019 Feb 25.

DOI:10.1016/j.bbrc.2019.02.110
PMID:30819403
Abstract

Long noncoding RNA ILF3-AS1 (ILF3-AS1) has been reported to be abnormally expressed in several tumors. However, its expression pattern and function in osteosarcoma have not been investigated. In this study, we showed that ILF3-AS1 expression was significantly up-regulated in both osteosarcoma tissues and cell lines. We first reported that ILF3-AS1 upregulation was induced by nuclear transcription factor SP1. Clinical assays revealed that higher expression of ILF3-AS1 was associated with advanced clinical stage, distant metastasis and shorter overall survival. in multivariate analysis, ILF3-AS1 expression level was found to be an independent prognostic factor for osteosarcoma patients. Functional investigations showed that knockdown of ILF3-AS1 suppressed the proliferation, migration and invasion of osteosarcoma cells, and promoted apoptosis. Bioinformatic software predicted that miR-212 both targeted the 3'-UTR of ILF3-AS1 and SOX5, which was confirmed using luciferase reporter assay, RT-PCR and Western blot. Taken together, ILF3-AS1 displayed its tumor-promotive roles in the progression of osteosarcoma through miR-212/SOX5 axis. Our findings help to elucidate the tumorigenesis of osteosarcoma, and future study will provide a novel therapeutic target for osteosarcoma.

摘要

长链非编码 RNA ILF3-AS1(ILF3-AS1)在几种肿瘤中被报道异常表达。然而,其在骨肉瘤中的表达模式和功能尚未被研究。在这项研究中,我们表明 ILF3-AS1 的表达在骨肉瘤组织和细胞系中均显著上调。我们首次报道 ILF3-AS1 的上调是由核转录因子 SP1 诱导的。临床检测表明,ILF3-AS1 的高表达与晚期临床分期、远处转移和总生存期缩短有关。在多变量分析中,ILF3-AS1 表达水平被发现是骨肉瘤患者的独立预后因素。功能研究表明,ILF3-AS1 的敲低抑制了骨肉瘤细胞的增殖、迁移和侵袭,并促进了细胞凋亡。生物信息学软件预测 miR-212 既靶向 ILF3-AS1 的 3'-UTR,也靶向 SOX5,这通过荧光素酶报告实验、RT-PCR 和 Western blot 得到了证实。总之,ILF3-AS1 通过 miR-212/SOX5 轴在骨肉瘤的进展中发挥其促进肿瘤的作用。我们的研究结果有助于阐明骨肉瘤的发生机制,未来的研究将为骨肉瘤提供新的治疗靶点。

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