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