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骨肉瘤中表达的微小RNA及其靶标的鉴定与验证

Identification and validation of microRNAs and their targets expressed in osteosarcoma.

作者信息

Zhang Can, Wan Jun, Long Feng, Liu Qing, He Hongbo

机构信息

Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Oncol Lett. 2019 Nov;18(5):5628-5636. doi: 10.3892/ol.2019.10864. Epub 2019 Sep 13.

Abstract

Osteosarcoma (OS) is the most common type of bone cancer in children and adolescents, and has a poor prognosis. Previous studies have demonstrated that a number of microRNAs (miRNAs) were deregulated in OS, and that the expression of certain miRNAs was correlated with the stage of OS. Therefore, miRNAs may serve a role as a diagnostic and prognostic biomarker of OS. miRNA and mRNA integrated analysis of public expression profiles in the Gene Expression Omnibus database for OS was performed, and the regulated targets of miRNA in OS were predicted. Next, the regulatory network of miRNAs/genes was constructed and verified by reverse transcription-quantitative polymerase chain reaction in tissues and MG-63 cell lines. Two miRNA expression profiling studies and four eligible mRNA expression profiling studies were selected. Ten upregulated miRNAs, 5 downregulated miRNAs and 5 DGEs were identified in OS compared with normal tissues. hsa-miR-346 was inversely correlated with the target gene c-FLIP, which was consistent with the results of integrated analysis. , pre-miRNA-346 can downregulate the protein expression of c-FLIP, while not changing the mRNA level of c-FLIP. In the regulatory network, hsa-miR-346 and its target gene, c-FLIP, can be used as biomarkers for an earlier diagnosis of OS.

摘要

骨肉瘤(OS)是儿童和青少年中最常见的骨癌类型,预后较差。先前的研究表明,一些微小RNA(miRNA)在骨肉瘤中表达失调,且某些miRNA的表达与骨肉瘤的分期相关。因此,miRNA可能作为骨肉瘤的诊断和预后生物标志物。对基因表达综合数据库中骨肉瘤的公共表达谱进行miRNA和mRNA综合分析,并预测骨肉瘤中miRNA的调控靶点。接下来,通过组织和MG-63细胞系中的逆转录-定量聚合酶链反应构建并验证miRNA/基因调控网络。选择了两项miRNA表达谱研究和四项合格的mRNA表达谱研究。与正常组织相比,在骨肉瘤中鉴定出10个上调的miRNA、5个下调的miRNA和5个差异基因表达。hsa-miR-346与靶基因c-FLIP呈负相关,这与综合分析结果一致。此外,pre-miRNA-346可下调c-FLIP的蛋白表达,而不改变c-FLIP的mRNA水平。在调控网络中,hsa-miR-346及其靶基因c-FLIP可作为骨肉瘤早期诊断的生物标志物。

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本文引用的文献

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Non-coding RNAs as a new dawn in tumor diagnosis.非编码 RNA 作为肿瘤诊断的新曙光。
Semin Cell Dev Biol. 2018 Jun;78:37-50. doi: 10.1016/j.semcdb.2017.07.035. Epub 2017 Jul 29.
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MicroRNAs and Potential Targets in Osteosarcoma: Review.微小 RNA 与骨肉瘤的潜在靶点:综述。
Front Pediatr. 2015 Aug 24;3:69. doi: 10.3389/fped.2015.00069. eCollection 2015.

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