MiR-96-5p promotes breast cancer migration by activating MEK/ERK signaling
MiR-96-5p promotes breast cancer migration by activating MEK/ERK signaling
复制标题
MiR-96-5p 通过激活 MEK/ERK 信号传导促进乳腺癌迁移
DOI：
10.1002/jgm.3188
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发表时间：
2020-04-13
影响因子：
3.5
通讯作者：
Jiang, Guo-qin
中科院分区：
文献类型：
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作者：
Qin, Wei-yan;Feng, Shi-chun;Jiang, Guo-qin
背景乳腺癌是全世界女性癌症死亡的主要原因。本研究的目的是探讨miR-96-5p在乳腺癌中的潜在作用。方法收集乳腺癌组织和匹配的癌旁组织。通过实时定量PCR（qRT-PCR）检测microRNA-96-5p（miR-96-5p）和精氨酸激酶3（AK3）的表达。通过Pearson卡方检验计算miR-96-5p和AK3之间的相关性。此外，应用miR-96-5p的模拟物或抑制剂来探讨miR-96-5p是否影响Transwell和伤口愈合实验中的迁移能力。通过TargetScan、miRDB和miRanda数据库进行生物信息学分析来鉴定miR-96-5p的靶基因。荧光素酶报告基因检测验证AK3为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的表达分别显着增加。 miR-96-5p的表达与AK3基因的表达呈负相关。 AK3 被证明是 miR-96-5p 的直接 mRNA 靶标。 AK3 与乳腺癌患者的总生存率呈正相关。 Kaplan-Meier 曲线和对数秩检验分析表明，AK3 水平降低与总生存率降低显着相关。 miR-96-5p 被证明可以通过 MEK/ERK 信号通路促进乳腺癌细胞的迁移。结论我们的结果确定了 miR-96-5p 通过靶向 AK3 激活 MEK/ERK 信号通路来促进乳腺癌细胞迁移。
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.