MicroRNA-188-5p inhibits the progression of breast cancer by targeting zinc finger protein 91

摘要

Breast cancer (BC) is the most commonly diagnosed malignant cancer in women. BC is the main cause of cancer-related death in women and seriously threatens the life and health of women worldwide. MicroRNAs (miRNAs/miRs) have been reported to regulate the development and progression of different types of cancer. However, the regulatory functions of miR-188-5p in BC have not been thoroughly demonstrated. In this present research, we identified that miR-188-5p was downregulated in BC tissues and several BC cell lines. Downregulation of miR-188-5p was significantly associated with advanced TNM stage. Moreover, we identified that miR-188-5p mimics significantly inhibited proliferation using CCK-8 assay, colony formation and xenograft animal model, suppressed invasion and migration detected by Transwell invasion assay, and increased the cellular apoptosis of BC cells as determined by cell apoptosis assay. Moreover miR-188-5p mimics also reduced the expression of NF-κB p65(Rel). To further investigate its regulatory mechanism, transcription factor zinc finger protein 91 (ZFP91) was predicted as the targeted protein of miR-188-5p by bioinformatic method. We confirmed their specific binding by dual luciferase (DLR) assay. We demonstrated that the overexpression of miR-188-5p significantly inhibited the expression of ZFP91 in BC cell lines and reduced the expression of NF-κB p65(Rel). An inverse correlation was found between the expression of miR-188-5p and ZFP91 in BC tissues. Importantly, we demonstrated that the restoration of ZFP91 was able to block the effect of miR-188-5p on the progression of MDA-MB-231 cells. Therefore, our study showed that miR-188-5p may be one of the important indicators and could inhibit the progression of human BC via targeting the ZFP91/NF-κB p65(Rel) signaling pathway, suggesting that miR-188-5p may be a promising future target for BC treatment.