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miR-425-5p 通过 Wnt/β-catenin 信号通路降低骨肉瘤中 LncRNA MALAT1 和 TUG1 的表达并抑制肿瘤发生。

miR-425-5p decreases LncRNA MALAT1 and TUG1 expressions and suppresses tumorigenesis in osteosarcoma via Wnt/β-catenin signaling pathway.

机构信息

Department of Emergency Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China.

Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China.

出版信息

Int J Biochem Cell Biol. 2019 Jun;111:42-51. doi: 10.1016/j.biocel.2019.04.004. Epub 2019 Apr 12.

Abstract

Multiple miRNAs have been recognized as critical regulators in osteosarcoma (OS) carcinogenesis. miR-425-5p was demonstrated to be downregulated in the serum of OS patients. However, the detailed roles of miR-425-5p in OS progression and its underlying molecular mechanism are far from being addressed. In our study, the reduced expression of miR-425-5p was observed in OS tissues and cells. Functional analyses showed that miR-425-5p overexpression suppressed OS cell proliferation, invasion and migration in vitro. Moreover, miR-425-5p upregulation decreased the expressions of MALAT1 and TUG1 in OS cells via directly binding them. miR-425-5p upregulation strikingly abrogated the activation of Wnt/β-catenin signaling pathway induced by MALAT1 and TUG1 overexpression in OS cells. Finally, we validated that miR-425-5p hindered OS tumor growth, and suppressed MALAT1 and TUG1 expressions and the Wnt/β-catenin signaling pathway in vivo. Our findings concluded that miR-425-5p suppressed the tumorigenesis of OS via decreasing MALAT1 and TUG1 expressions through inactivation of the Wnt/β-catenin signaling pathway, contributing to a better understanding of the molecular mechanism of the tumorigenesis of OS.

摘要

多种 microRNA 已被证实为骨肉瘤(OS)发生发展的关键调控因子。miR-425-5p 在 OS 患者的血清中被证明下调。然而,miR-425-5p 在 OS 进展中的详细作用及其潜在的分子机制仍有待解决。在我们的研究中,观察到 OS 组织和细胞中 miR-425-5p 的表达降低。功能分析表明,miR-425-5p 的过表达抑制了 OS 细胞在体外的增殖、侵袭和迁移。此外,miR-425-5p 的上调通过直接结合它们来降低 OS 细胞中 MALAT1 和 TUG1 的表达。miR-425-5p 的上调显著阻断了 MALAT1 和 TUG1 过表达诱导的 OS 细胞中 Wnt/β-catenin 信号通路的激活。最后,我们验证了 miR-425-5p 在体内抑制 OS 肿瘤生长,并抑制 MALAT1 和 TUG1 的表达以及 Wnt/β-catenin 信号通路。我们的研究结果表明,miR-425-5p 通过抑制 MALAT1 和 TUG1 的表达,从而抑制 OS 的肿瘤发生,通过失活 Wnt/β-catenin 信号通路,为更好地理解 OS 肿瘤发生的分子机制做出了贡献。

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