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微小 RNA-520a-3p 通过 PI3K/AKT/mTOR 信号通路抑制非小细胞肺癌细胞生长和转移。

MicroRNA-520a-3p inhibits cell growth and metastasis of non-small cell lung cancer through PI3K/AKT/mTOR signaling pathway.

机构信息

Department of Respiratory, Linyi People's Hospital, Linyi, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Apr;22(8):2321-2327. doi: 10.26355/eurrev_201804_14822.

Abstract

OBJECTIVE

MicroRNAs are a class of small non-coding RNAs that be involved in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the effects of miR-520a-3p in cell growth and metastasis.

MATERIALS AND METHODS

The mimics and inhibitor of miR-520a-3p were used to identify the effects of miR-520a-3p on cell proliferation and apoptosis using methylthiazol tetrazolium (MTT) assay and flow-cytometric method, respectively. Transwell assay was used to evaluate the cell migration and invasion. The protein expression levels related PI3K/AKT/mTOR signaling pathways were measured by Western blot.

RESULTS

The results showed that miR-520a-3p overexpression could significantly inhibit cell proliferation and induce apoptosis, suppress cell migration and invasion. MiR-520a-3p overexpression could markedly reduce the ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) compared with control. However, miR-520a-3p overexpression could increase caspase-3 expression compared with control group. After inhibited the expression of miR-520a-3p, the capacity of cell proliferation, migration and invasion were increased, cell apoptosis was inhibited compared with control group. The ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, MMP-2 and MMP-9 were increased compared with control group.

CONCLUSIONS

Our study suggested that miR-520a-3p could suppress the NSCLC proliferation, migration and invasion through PI3K/AKT/mTOR signaling pathway.

摘要

目的

微小 RNA 是一类参与非小细胞肺癌(NSCLC)发病机制的小非编码 RNA。本研究旨在评估 miR-520a-3p 在细胞生长和转移中的作用。

材料与方法

使用 miR-520a-3p 的模拟物和抑制剂,通过噻唑蓝(MTT)检测法和流式细胞术分别鉴定 miR-520a-3p 对细胞增殖和凋亡的影响。采用 Transwell 测定法评估细胞迁移和侵袭。通过 Western blot 测定法测定与 PI3K/AKT/mTOR 信号通路相关的蛋白表达水平。

结果

结果表明,miR-520a-3p 过表达可显著抑制细胞增殖并诱导细胞凋亡,抑制细胞迁移和侵袭。miR-520a-3p 过表达可使 p-AKT/AKT、p-PI3K/PI3K 和 Bcl-2/Bax 的比值、mTOR、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的水平明显降低,与对照组相比。然而,miR-520a-3p 过表达可使 caspase-3 的表达水平高于对照组。抑制 miR-520a-3p 的表达后,与对照组相比,细胞增殖、迁移和侵袭的能力增加,细胞凋亡受到抑制。p-AKT/AKT、p-PI3K/PI3K 和 Bcl-2/Bax 的比值、mTOR、MMP-2 和 MMP-9 的水平升高,与对照组相比。

结论

本研究表明,miR-520a-3p 可通过 PI3K/AKT/mTOR 信号通路抑制 NSCLC 的增殖、迁移和侵袭。

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