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miR-1285-3p 是人类骨肉瘤的一个潜在预后标志物,通过靶向 YAP1 发挥肿瘤抑制作用。

miR-1285-3p is a potential prognostic marker in human osteosarcoma and functions as a tumor suppressor by targeting YAP1.

出版信息

Cancer Biomark. 2019;25(1):1-10. doi: 10.3233/CBM-180013.

Abstract

BACKGROUND

Despite the major advances in the treatment, the overall survival of osteosarcoma remains poor. MicroRNAs (miRNAs) are involved in tumorigenesis and progression though modulating their target genes. In the present study, the roles of miR-1285-3p in osteosarcoma was investigated.

METHODS

Microarray profiling was applied to distinguish the up and down regulated microRNAs in osteosarcoma. Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of miR-1285-3p and YAP1 expression. MTT and transwell assays were carried out to determine the cells proliferation and invasion respectively. Moreover, dual luciferase reporter assay was performed to evaluate the binding efficiency between miR-1285-3p and the 3'UTR of YAP1.

RESULTS

MiR-1285-3p was down regulated in osteosarcoma tissues and cell lines and the reduction of miR-1285-3p expression predicted a poor overall survival of osteosarcoma patients. Ectopic expression of miR-1285-3p inhibited osteosarcoma cell proliferation, colony formation and invasion. In addition, YAP1 was further demonstrated as a direct target of miR-1285-3p. Moreover, overexpression of YAP1 reversed the inhibitory effects of miR-1285-3p on osteosarcoma cells proliferation and invasion.

CONCLUSIONS

MiR-1285-3p which was low expressed in osteosarcoma inhibited the proliferation and invasion of osteosarcoma cells via direct targeting YAP1. These results suggested that miR-1285-3p might be a potential therapeutic targets and biomarker in osteosarcoma.

摘要

背景

尽管在治疗方面取得了重大进展,但骨肉瘤的总体生存率仍然较差。 microRNAs(miRNAs)通过调节其靶基因参与肿瘤发生和进展。本研究探讨了 miR-1285-3p 在骨肉瘤中的作用。

方法

应用微阵列分析区分骨肉瘤中上调和下调的 microRNAs。通过定量实时 PCR(qRT-PCR)检测 miR-1285-3p 和 YAP1 表达。MTT 和 Transwell 测定分别用于测定细胞增殖和侵袭。此外,双荧光素酶报告基因测定用于评估 miR-1285-3p 与 YAP1 的 3'UTR 之间的结合效率。

结果

miR-1285-3p 在骨肉瘤组织和细胞系中下调,miR-1285-3p 表达的降低预示着骨肉瘤患者总体生存率较差。过表达 miR-1285-3p 抑制骨肉瘤细胞增殖、集落形成和侵袭。此外,进一步证实 YAP1 是 miR-1285-3p 的直接靶标。此外,过表达 YAP1 逆转了 miR-1285-3p 对骨肉瘤细胞增殖和侵袭的抑制作用。

结论

在骨肉瘤中低表达的 miR-1285-3p 通过直接靶向 YAP1 抑制骨肉瘤细胞的增殖和侵袭。这些结果表明,miR-1285-3p 可能是骨肉瘤的潜在治疗靶点和生物标志物。

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