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miR-487b 和 TRAK2 形成轴调控骨肉瘤的侵袭性,是潜在的治疗靶点和预后生物标志物。

miR-487b and TRAK2 that form an axis to regulate the aggressiveness of osteosarcoma, are potential therapeutic targets and prognostic biomarkers.

机构信息

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

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

出版信息

J Biochem Mol Toxicol. 2020 Aug;34(8):e22511. doi: 10.1002/jbt.22511. Epub 2020 Apr 8.

DOI:10.1002/jbt.22511
PMID:32267991
Abstract

To investigate the effect of microRNA-487b (miR-487b) as well as the underlying mechanism in osteosarcoma (OS). Data downloaded from the Gene Expression Omnibus (GEO) database were used to analyze the expression and prognostic value of miR-487b/TRAK2. Cell counting kit-8, colony formation, and transwell assays were performed to investigate the biological functions of miR-487b and TRAK2. Luciferase reporter assay was applied to confirm the interactions between miR-487b and TRAK2. miR-487b was overexpressed in OS tissues and was inversely associated with the prognosis of OS patients. We discovered that miR-487b could contribute to the proliferative, clonogenic, invasive, and migratory capabilities of OS cells. Through target prediction using miRWalk and differential expression analysis based on the GEO data set, trafficking kinesin protein 2 (TRAK2) was recognized as a potential target of miR-487b, which was further verified by luciferase reporter assay. The expression of TRAK2 was decreased in OS tissues compared with normal tissues and was positively correlated with the prognosis of OS patients. A negative relevance was presented between the expression of miR-487b and TRAK2 in OS cells. Of note, further mechanistic analyses indicated that TRAK2 was implicated in the regulatory effect of miR-487b on the cell malignant behaviors in OS. To sum up, these results demonstrated that miR-487b played an oncogenic role in OS progression via directly targeting TRAK2, which could advance the development of cancer treatment.

摘要

目的

研究微小 RNA-487b(miR-487b)及其在骨肉瘤(OS)中的潜在机制。

方法

从基因表达综合数据库(GEO)下载数据,分析 miR-487b/TRAK2 的表达及预后价值。细胞计数试剂盒-8、集落形成和 Transwell 分析用于研究 miR-487b 和 TRAK2 的生物学功能。应用荧光素酶报告实验验证 miR-487b 和 TRAK2 之间的相互作用。

结果

miR-487b 在 OS 组织中过表达,与 OS 患者的预后呈负相关。我们发现 miR-487b 可促进 OS 细胞的增殖、集落形成、侵袭和迁移能力。通过 miRWalk 进行靶基因预测和 GEO 数据集差异表达分析,鉴定出 TRAK2 是 miR-487b 的一个潜在靶点,该结果进一步通过荧光素酶报告实验验证。与正常组织相比,TRAK2 在 OS 组织中的表达降低,且与 OS 患者的预后呈正相关。miR-487b 在 OS 细胞中的表达与 TRAK2 呈负相关。值得注意的是,进一步的机制分析表明,TRAK2 参与了 miR-487b 对 OS 细胞恶性行为的调控作用。

结论

综上所述,miR-487b 通过直接靶向 TRAK2 在 OS 进展中发挥致癌作用,这可能有助于癌症治疗的发展。

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