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长链非编码 RNA PCAT-1 通过 miR-508-3p/ZEB1 轴促进骨肉瘤的进展。

LncRNA PCAT-1 promotes the progression of osteosarcoma via miR-508-3p/ZEB1 axis.

机构信息

Department of Orthopedics (II), Jiyang People's Hospital, Jinan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Mar;25(6):2517-2527. doi: 10.26355/eurrev_202103_25415.

Abstract

OBJECTIVE

Osteosarcoma (OS) is an adolescent idiopathic malignancy with a poor prognosis. Accumulating evidence has verified that long non-coding RNAs (lncRNAs) were implicated in the initiation and development of various tumors. We aimed to clarify the functions and underlying mechanism of lncRNA PCAT-1 in OS progression.

PATIENTS AND METHODS

RT-qPCR was performed to examine the relative expressions of PCAT-1, miR-508-3p and ZEB1 in OS tissues or cells. The proliferation capacities of OS cells with different transfection were detected by CCK-8 assays. Transwell assays were carried out to determine the functions of PCAT-1 and miR-508-3p in OS cell migration and invasion. Moreover, bioinformatical analysis and Luciferase reporter assay were applied to verify the association between PCAT-1 and miR-508-3p, miR-508-3p and ZEB1.

RESULTS

Data of current study revealed that PCAT-1 was markedly upregulated in OS, which indicated poor prognosis of OS patients. CCK-8 and transwell assays indicated that PCAT-1 upregulation could promote OS cell proliferation, invasion and migration. Additionally, we found that miR-508-3p was a direct target of PCAT-1, and PCAT-1 regulated the development of OS via decreasing miR-508-3p and activating its target gene ZEB1.

CONCLUSIONS

All data demonstrated that PCAT-1 promoted OS progression, and miR-508-3p/ZEB1 axis was implicated in the functional roles of PCAT-1 in OS, suggesting that PCAT-1/miR-508-3p/ZEB1 might serve as candidate therapeutic targets for OS patients.

摘要

目的

骨肉瘤(OS)是一种青少年特发性恶性肿瘤,预后较差。越来越多的证据证实,长链非编码 RNA(lncRNA)参与了各种肿瘤的发生和发展。本研究旨在阐明 lncRNA PCAT-1 在 OS 进展中的作用和潜在机制。

患者和方法

采用 RT-qPCR 检测 OS 组织或细胞中 PCAT-1、miR-508-3p 和 ZEB1 的相对表达。通过 CCK-8 检测不同转染的 OS 细胞的增殖能力。通过 Transwell 测定法检测 PCAT-1 和 miR-508-3p 在 OS 细胞迁移和侵袭中的作用。此外,应用生物信息学分析和荧光素酶报告基因检测验证 PCAT-1 与 miR-508-3p、miR-508-3p 与 ZEB1 之间的关联。

结果

本研究数据表明,PCAT-1 在 OS 中明显上调,表明 OS 患者的预后较差。CCK-8 和 Transwell 测定表明,PCAT-1 上调可促进 OS 细胞增殖、侵袭和迁移。此外,我们发现 miR-508-3p 是 PCAT-1 的直接靶标,PCAT-1 通过降低 miR-508-3p 并激活其靶基因 ZEB1 来调节 OS 的发生发展。

结论

所有数据表明,PCAT-1 促进了 OS 的进展,miR-508-3p/ZEB1 轴参与了 PCAT-1 在 OS 中的功能作用,提示 PCAT-1/miR-508-3p/ZEB1 可能成为 OS 患者的候选治疗靶点。

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