MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

• DOI: 10.18632/oncotarget.15214
• Publication Date: 2017-02-15T19:17:50Z
• Authors: Saber Imani; Chunli Wei; Jingliang Cheng; Md. Asaduzzaman Khan; Shangyi Fu; Luquan Yang; Mousumi Tania; Xianqin Zhang; Xiuli Xiao; Xianning Zhang; Junjiang Fu
• Keywords: Ectopic expression; Slug

MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and progression of cancer metastasis. Here, we analyzed the expression, targets functional effects miR-34a on epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs), such as TWIST1, SLUG ZEB1/2, EMT-inducing protein NOTCH1 in breast (BC) cell migration invasion its correlation with clinical outcomes. Expression is downregulated human metastatic cancers (MBC) compared normal tissues negatively correlated clinicopathological features MBC patients. Ectopic expression cell-line BT-549 significantly inhibits invasion, but exhibits no clear effect BC growth. We found that able inactivate EMT signaling pathway mediatory NOTCH1, ZEB1 upon 3'-UTR activity lines, has inhibitory ZEB2. Furthermore, investigated synergistic Thymoquinone (TQ) together EMT-associated proteins. Results showed co-delivery TQ by directly targeting TWIST1 line, indicating they might be a promising therapeutic combination Epigenetic inactivation EMT-TFs/miR-34a can potentially alter equilibrium these regulations, facilitating metastasis BC. Altogether, our findings suggest alone could serve potential agent for MBC, TQ, their synergistically enhanced.