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miR-182-3p 通过靶向 EBF2 对骨肉瘤的潜在调控作用。

Potential Regulatory Effects of miR-182-3p in Osteosarcoma via Targeting EBF2.

机构信息

Department of Orthopedics, the Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin 130041, China.

Research Centre of the Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin 130041, China.

出版信息

Biomed Res Int. 2019 Mar 12;2019:4897905. doi: 10.1155/2019/4897905. eCollection 2019.

DOI:10.1155/2019/4897905
PMID:30993113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6434304/
Abstract

Osteosarcoma (OS) is one of the most common primary malignant bone tumors in adolescents with a high mortality rate. MicroRNA (miRNA) is a kind of noncoding RNAs and has been proved to participate in many physiological processes. Many miRNAs have been reported to act as function regulators in OS. In our study, the miRNA and gene expression profiles of OS were downloaded from GEO Datasets and the differential expression analysis was performed using GEO2R. 58 up- and 126 downregulated miRNAs were found. In the three OS gene profiles, 125 up- and 27 downregulated genes were found to be differentially expressed in at least two profiles. The miRNA-mRNA networks were constructed to predict the potential target genes of 10 most up- and downregulated miRNA. Venn analysis was used to detect the coexpressed differentially expressed genes (DEGs). EBF2, one of the upregulated DEGs, was also a potential target gene of miR-182-3p. Knockdown and overexpression of miR-182-3p resulted in overexpression and downexpression of EBF2 separately. Luciferase reporter gene experiment further verified the binding site of miR-182-3p and EBF2. CCK8 assay showed that miR-182-3p knockdown can further enhance the proliferation activity of OS cells, while overexpressing miR-182-3p can inhibit the proliferation activity of OS cells. Our research indicated that downexpression of miR-182-3p in OS cells results in overexpression of EBF2 and promotes the progression of OS.

摘要

骨肉瘤(OS)是青少年中最常见的原发性恶性骨肿瘤之一,死亡率很高。微小 RNA(miRNA)是一种非编码 RNA,已被证明参与许多生理过程。许多 miRNA 已被报道在 OS 中作为功能调节剂发挥作用。在我们的研究中,从 GEO 数据集下载了 OS 的 miRNA 和基因表达谱,并使用 GEO2R 进行了差异表达分析。发现了 58 个上调和 126 个下调 miRNA。在三个 OS 基因谱中,发现了 125 个上调和 27 个下调基因在至少两个谱中差异表达。构建了 miRNA-mRNA 网络,以预测 10 个上调和下调 miRNA 的潜在靶基因。Venn 分析用于检测共表达的差异表达基因(DEG)。上调的 DEG 之一 EBF2 也是 miR-182-3p 的潜在靶基因。miR-182-3p 的敲低和过表达分别导致 EBF2 的过表达和下调。荧光素酶报告基因实验进一步验证了 miR-182-3p 和 EBF2 的结合位点。CCK8 assay 表明,miR-182-3p 的敲低可以进一步增强 OS 细胞的增殖活性,而过表达 miR-182-3p 可以抑制 OS 细胞的增殖活性。我们的研究表明,OS 细胞中 miR-182-3p 的下调导致 EBF2 的过表达,并促进 OS 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5539/6434304/2b0dace2a0ac/BMRI2019-4897905.008.jpg
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