Mechanism of microRNA-141 regulates epithelial-mesenchymal transition in breast cancer by targeting epidermal growth factor receptor

Objective To screen and investigate the expression levels of microRNA-141 (miR-141) and epidermal growth factor receptor (EGFR) in breast cancer cells and their effects on epithelial-mesenchymal transition, cell migration and invasion through bioinformatics.

Methods Microarray analysis was used to screen differentially expressed genes; the weighted gene co-expression network analysis (WGCNA) and protein-protein interaction network of genes were used to identify key genes of breast cancer; the real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expressions of miR-141 and EGFR in breast cancer tissues and cells; the Targetscan and Miranda were used to predict the target relationship between miR-141 and EGFR, and the target relationship between them was verified by dual luciferase reporter gene detection; the Transwell assay was used to evaluate migration ability of cells; the cell viability was detected by CCK-8 method; the western blot was used to detect the expressions of E-cadherin and vimentin.

Results The results of gene expression heat map and WGCNA analysis showed that EGFR was significantly highly expressed in tumor tissues. It was verified by molecular biology that the expression of miR-141 was significantly down-regulated and the expression of EGFR was significantly up-regulated in breast cancer tissues and cells (P < 0.05). Dual luciferase reporter gene detection found that EGFR was a target gene of miR-141, and was regulated by miR-141 expression in breast cancer cells. Cell experiments showed that the migration and proliferation of breast cancer cells were inhibited in miR-141 overexpression group, while the opposite results were observed in the EGFR group, and there were significant differences between two groups (P < 0.05). Overexpression of miR-141 was able to significantly promote the expression of E-cadherin and significantly inhibit the expression of Vimentin (P < 0.05), indicating that overexpression of miR-141 can inhibit the process of epithelial-mesenchymal transition of tumor cells.

Conclusion The miR-141 can inhibit the proliferation of breast cancer cells and regulate progress of epithelial-mesenchymal transition by targeting EGFR.