Guo Jingyun, Luo Can, Yang Yuqin, Dong Jianyu, Guo Zhaoze, Yang Jinlamao, Lian Huining, Ye Changsheng, Liu Minfeng
Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
Cancer Manag Res. 2021 Jan 15;13:403-413. doi: 10.2147/CMAR.S279747. eCollection 2021.
Large amounts of microRNAs (miRNAs) have been reported to be aberrantly expressed in malignant cancers. MiR-491-5p makes a significant contribution to the inhibition of multiple cancer processes. However, the specific mechanism and function of miR-491-5p and in breast cancer (BC) is still not fully elucidated.
MiR-491-5p and ZNF-703 expressions or gene transfection effects were identified by RT-qPCR or Western blot in BC tissues or cells. And ZNF-703 expression was monitored through immunohistochemistry method. Cellular function was also confirmed using Transwell assay. Besides, AKT/mTOR pathway-related proteins were analyzed using Western blotting analysis. Moreover, the interplay between miR-491-5p and ZNF-703 was verified through dual-luciferase reporter assay.
miR-491-5p was lowly expressed, ZNF-703 was highly expressed in BC, and miR-491-5p with low expression and ZNF-703 with high expression were associated with poor prognosis of BC patients. Results of cellular function revealed that overexpression of miR-491-5p markedly suppressed BC cell migration and invasion, and knockdown of miR-491-5p had the opposite effect. Besides, mechanism research disclosed that miR-491-5p directly could bind to ZNF-703 and downregulate ZNF-703. Moreover, we proved that ZNF-703 could prominently reverse the influences of miR-491-5p on the migration and invasion of BC cells. More importantly, the data revealed that miR-491-5p repressed AKT/mTOR pathway by ZNF-703 in BC cells.
MiR-491-5p prominently suppresses the metastasis of BC cells through ZNF-703 to regulate AKT/mTOR pathway, indicating that miR-491-5p and ZNF-703 might be served as the potential therapeutic targets for BC.
大量的微小RNA（miRNA）已被报道在恶性肿瘤中异常表达。MiR-491-5p对多种癌症进程的抑制作用显著。然而，miR-491-5p在乳腺癌（BC）中的具体机制和功能仍未完全阐明。
通过RT-qPCR或蛋白质免疫印迹法在BC组织或细胞中鉴定miR-491-5p和ZNF-703的表达或基因转染效果。并通过免疫组织化学方法监测ZNF-703的表达。还使用Transwell实验确认细胞功能。此外，通过蛋白质免疫印迹分析来分析AKT/mTOR通路相关蛋白。此外，通过双荧光素酶报告基因实验验证miR-491-5p与ZNF-703之间的相互作用。
miR-491-5p在BC中低表达，ZNF-703高表达，且miR-491-5p低表达和ZNF-703高表达与BC患者的不良预后相关。细胞功能结果显示，miR-491-5p的过表达显著抑制BC细胞的迁移和侵袭，而敲低miR-491-5p则具有相反的效果。此外，机制研究表明，miR-491-5p可以直接与ZNF-703结合并下调ZNF-703。此外，我们证明ZNF-703可以显著逆转miR-491-5p对BC细胞迁移和侵袭的影响。更重要的是，数据显示miR-491-5p在BC细胞中通过ZNF-703抑制AKT/mTOR通路。
MiR-491-5p通过ZNF-703显著抑制BC细胞的转移以调节AKT/mTOR通路，表明miR-491-5p和ZNF-703可能作为BC的潜在治疗靶点。
