DownRegulation of miR200c and UpRegulation of miR30c Target both Stemness and Metastasis Genes in Breast Cancer

Objective microRNAs (miRNAs) play important role in progression of tumorigenesis. They can target selfrenewal and epithelialmesenchymal 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 selfrenewal 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 MCF7 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 selfrenewal 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 MCF7 cells (P 0.05). Additionally, they had enhanced migration and invasive capabilities. Our computational analyses determined that miR200c and miR30c could be candidates for targeting both stemness and EMT pathways. Expression level of miR200c was reduced, while miR30c expression level was enhanced in mammospheres, similar to the breast tumor tissues isolated from three patients with grade II/III who received neoadjuvant treatment. Expression level of putative stem cell markers (OCT4, SOX2, cMYC) and EMTrelated genes (SNAIL1, CDH2, TWIST1/2) were also significantly increased in mammospheres and three indicated patients (P 0.05). ConclusionSimultaneous downregulation and upregulation of respectively miR200c and miR30c might be signature of BCSC enrichment in patients post neoadjuvant therapy. Therefore, targeting both miR200c and miR30c could be useful for developing new therapeutic approaches, against BCSCs.