Down-Regulation of miR-200c and Up-Regulation of miR-30c Target both Stemness and Metastasis Genes in Breast Cancer.

OBJECTIVE

microRNAs (miRNAs) play important role in progression of tumorigenesis. They can target self-renewal and epithelial-mesenchymal transition (EMT) abilities in tumor cells, especially in cancer stem cells (CSCs). The objective of this study was to implement data mining to identify important miRNAs for targeting both self-renewal and EMT. We also aimed to evaluate these factors in mammospheres as model of breast cancer stem cells (BCSCs) and metastatic tumor tissues.

MATERIALS AND METHODS

In this experimental study, mammospheres were derived from MCF-7 cells and characterized for the CSCs properties. Then expression pattern of the selected miRNAs in spheroids were evaluated, using the breast tumor cells obtained from seven patients. Correlation of miRNAs with self-renewal and EMT candidate genes were assessed in mammospheres and metastatic tumors.

RESULTS

The results showed that mammospheres represented more colonogenic and spheroid formation potential than MCF-7 cells (P<0.05). Additionally, they had enhanced migration and invasive capabilities. Our computational analyses determined that and could be candidates for targeting both stemness and EMT pathways. Expression level of was reduced, while expression level was enhanced in mammospheres, similar to the breast tumor tissues isolated from three patients with grade II/III who received neo-adjuvant treatment. Expression level of putative stem cell markers () and EMT-related genes () were also significantly increased in mammospheres and three indicated patients (P<0.05).

CONCLUSION

Simultaneous down-regulation and up-regulation of respectively and might be signature of BCSC enrichment in patients post neo-adjuvant therapy. Therefore, targeting both and could be useful for developing new therapeutic approaches, against BCSCs.