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微小 RNA-185 通过靶向囊泡相关膜蛋白 2 抑制人骨肉瘤 MG63 细胞的增殖、迁移和侵袭。

MicroRNA-185 inhibits proliferation, migration and invasion in human osteosarcoma MG63 cells by targeting vesicle-associated membrane protein 2.

机构信息

Department of Orthopedics, Zhoukou Central Hospital, Zhoukou City, Henan Province, 466000, PR China.

Department of Orthopedics, Zhoukou Central Hospital, Zhoukou City, Henan Province, 466000, PR China.

出版信息

Gene. 2019 May 15;696:80-87. doi: 10.1016/j.gene.2019.01.034. Epub 2019 Feb 2.

Abstract

MicroRNAs (miRNAs) play an essential role in cancer development. Several studies have indicated that miRNAs mediate tumorigenesis processes, such as inflammation, proliferation, apoptosis and invasion. In the present study, we aimed to investigate the role of the microRNA-185 (miR-185) on the proliferation, migration and invasion of osteosarcoma (OS). MiR-185 expression was reduced in OS tissues and OS cell lines. MiR-185 inhibited OS cell proliferation, migration and invasion. Furthermore, a dual-luciferase assay validated that vesicle-associated membrane protein 2 (VAMP2) was a direct target of miR-185. Overexpression of miR-185 in OC cells reduced VAMP2 expression in protein and mRNA levels, whereas suppression of miR-185 led to an increase in VAMP2 protein and mRNA levels. In addition, we found that VAMP2 silencing inhibited the OS cell proliferation, migration and invasion. Further studies verified that introducing VAMP2 mRNA into cells over-expressing miR-185 abrogated the effects of miR-185 on OS cell proliferation, migration and invasion. Therefore, these results confirm that decreased expression of miR-185 might be regarded as a tumor marker for the early diagnosis of OS, by manipulating of its interactive factors with VAMP2, to provide an effective novel therapeutic target for treatment of the OS tumor.

摘要

微小 RNA(miRNAs)在癌症发展中起着至关重要的作用。有几项研究表明,miRNAs 介导肿瘤发生过程,如炎症、增殖、凋亡和侵袭。在本研究中,我们旨在研究微小 RNA-185(miR-185)对骨肉瘤(OS)增殖、迁移和侵袭的作用。miR-185 在 OS 组织和 OS 细胞系中的表达降低。miR-185 抑制 OS 细胞的增殖、迁移和侵袭。此外,双荧光素酶报告基因实验验证了囊泡相关膜蛋白 2(VAMP2)是 miR-185 的直接靶标。在 OC 细胞中转染 miR-185 后,VAMP2 的表达在蛋白和 mRNA 水平上均降低,而抑制 miR-185 则导致 VAMP2 蛋白和 mRNA 水平升高。此外,我们发现 VAMP2 沉默抑制了 OS 细胞的增殖、迁移和侵袭。进一步的研究证实,将 VAMP2 mRNA 导入 miR-185 过表达的细胞中,可消除 miR-185 对 OS 细胞增殖、迁移和侵袭的影响。因此,这些结果证实,miR-185 的表达降低可能被视为 OS 早期诊断的肿瘤标志物,通过操纵其与 VAMP2 的相互作用因子,为 OS 肿瘤的治疗提供一种有效的新的治疗靶点。

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