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miR-96-5p 通过激活 MEK/ERK 信号促进乳腺癌迁移。

MiR-96-5p promotes breast cancer migration by activating MEK/ERK signaling.

机构信息

Department of Surgery, The Second Affiliated Hospital of Soochow University, China.

Department of General Surgery, The First People's Hospital of Nantong, China.

出版信息

J Gene Med. 2020 Aug;22(8):e3188. doi: 10.1002/jgm.3188. Epub 2020 Apr 13.

Abstract

BACKGROUND

Breast cancer is the leading cause of cancer deaths in women worldwide. The purpose of the current study was to investigate the potential role of miR-96-5p in breast cancer.

METHODS

Breast cancer tissues and matched para-cancerous tissues were collected. The expression of microRNA-96-5p (miR-96-5p) and arginine kinase 3 (AK3) was detected by quantitative real-time PCR (qRT-PCR). The correlation between miR-96-5p and AK3 was calculated by Pearson's Chi-square test. Moreover, mimics or inhibitors of miR-96-5p were applied to explore whether miR-96-5p influences the migration capacity in Transwell and wound healing assays. Bioinformatics analysis was performed to identify the target genes of miR-96-5p through the TargetScan, miRDB and miRanda databases. A luciferase reporter assay was performed to verify AK3 as a downstream target gene of miR-96-5p.

RESULTS

The expression of miR-96-5p was significantly increased in breast cancer tissue and breast cancer cell lines compared with para-cancerous tissue and a breast cell line, respectively. The expression of miR-96-5p negatively correlated with AK3 gene expression. AK3 was demonstrated to be a direct mRNA target of miR-96-5p. AK3 was positively associated with the overall survival of breast cancer patients. Kaplan-Meier curve and log rank test analyses revealed that decreased AK3 levels were significantly associated with reduced overall survival. miR-96-5p was shown to promote the migration of breast cancer cells through the MEK/ERK signaling pathway.

CONCLUSION

Our results identify a role for miR-96-5p in promoting breast cancer cell migration through activation of MEK/ERK signaling by targeting AK3.

摘要

背景

乳腺癌是全球女性癌症死亡的主要原因。本研究旨在探讨 microRNA-96-5p(miR-96-5p)在乳腺癌中的潜在作用。

方法

收集乳腺癌组织和配对癌旁组织。采用实时定量 PCR(qRT-PCR)检测 microRNA-96-5p(miR-96-5p)和精氨酸激酶 3(AK3)的表达。采用 Pearson's Chi-square 检验计算 miR-96-5p 与 AK3 的相关性。此外,应用 miR-96-5p 的模拟物或抑制剂,通过 Transwell 和划痕愈合实验探讨 miR-96-5p 是否影响迁移能力。通过 TargetScan、miRDB 和 miRanda 数据库进行生物信息学分析,以确定 miR-96-5p 的靶基因。通过荧光素酶报告基因实验验证 AK3 是 miR-96-5p 的下游靶基因。

结果

与癌旁组织和乳腺细胞系相比,乳腺癌组织和乳腺癌细胞系中 miR-96-5p 的表达明显增加。miR-96-5p 的表达与 AK3 基因表达呈负相关。AK3 被证明是 miR-96-5p 的直接 mRNA 靶基因。AK3 与乳腺癌患者的总生存期呈正相关。Kaplan-Meier 曲线和对数秩检验分析表明,AK3 水平降低与总生存期缩短显著相关。miR-96-5p 通过 MEK/ERK 信号通路促进乳腺癌细胞的迁移。

结论

本研究结果表明,miR-96-5p 通过靶向 AK3 激活 MEK/ERK 信号通路,在促进乳腺癌细胞迁移中发挥作用。

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