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微小RNA-508-5p通过靶向S期激酶相关蛋白2抑制人胃癌转移。

MicroRNA-508-5p suppresses metastasis in human gastric cancer by targeting S-phase kinase‑associated protein 2.

作者信息

Duan Xiangguo, Bai Jing, Wei Jun, Li Zhenhao, Liu Xinlan, Xu Guangxian

机构信息

Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.

Department of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):2163-2171. doi: 10.3892/mmr.2017.6793. Epub 2017 Jun 15.

Abstract

S-phase kinase-associated protein 2 (SKP2), a potent oncogene was revealed to be upregulated in gastric cancer (GC) tissue samples, in which SKP2 was inversely correlated with microRNA (miR)‑508‑5p transcripts. In present study, the functional effect of miR‑508‑5p on SKP2 and its metastatic potential were investigated in SGC‑7901 GC cells. Significant downregulation of the miR‑508‑5p transcript was associated with the progression of GC. Furthermore, the overexpression of miR‑508‑5p was demonstrated to inhibit the proliferation, migration and invasion of SGC‑7901 cells, as well as induced cell apoptosis and cell cycle arrest at the G0/G1 phase in vitro. The overexpression of miR‑508‑5p was able to downregulate the expression of the SKP2 oncogene, through a mechanism by which miR‑508‑5p directly targeted the SKP2 gene. Thus, regulating transcriptional and post‑transcriptional SKP2 expression, as demonstrated using luciferase reporter assays, reverse transcription‑quantitative polymerase chain reaction analysis and immunoblotting assays. The results of the present study identified that miR‑508‑5p functionally affects the SKP2 gene and reduces metastatic potential in GC, suggesting a novel role of miR‑508‑5p in the regulation of SKP2 and cell cycle.

摘要

S期激酶相关蛋白2(SKP2)是一种强效癌基因,在胃癌(GC)组织样本中呈上调,其中SKP2与微小RNA(miR)-508-5p转录本呈负相关。在本研究中,在SGC-7901胃癌细胞中研究了miR-508-5p对SKP2的功能影响及其转移潜能。miR-508-5p转录本的显著下调与胃癌的进展相关。此外,miR-508-5p的过表达被证明可抑制SGC-7901细胞的增殖、迁移和侵袭,并在体外诱导细胞凋亡和细胞周期停滞于G0/G1期。miR-508-5p的过表达能够下调SKP2癌基因的表达,其机制是miR-508-5p直接靶向SKP2基因。因此,通过荧光素酶报告基因检测、逆转录-定量聚合酶链反应分析和免疫印迹分析证明,miR-508-5p可调节SKP2的转录和转录后表达。本研究结果表明,miR-508-5p在功能上影响SKP2基因并降低胃癌的转移潜能,提示miR-508-5p在调节SKP2和细胞周期中具有新作用。

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