Abstract
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 miR-200c and miR-30c could be candidates for targeting both stemness and EMT pathways.
Expression level of miR-200c was reduced, while miR-30c 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 (OCT4, SOX2, c-MYC) and EMT-related genes (SNAIL1, CDH2, TWIST1/2) were
also significantly increased in mammospheres and three indicated patients (P<0.05).
Conclusion: Simultaneous down-regulation and up-regulation of respectively miR-200c and miR-30c might be
signature of BCSC enrichment in patients post neo-adjuvant therapy. Therefore, targeting both miR-200c and miR-30c
could be useful for developing new therapeutic approaches, against BCSCs.
Citation
ID:
152743
Ref Key:
rahimi2019celldown-regulation