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


Mahsa Rahimi, M.Sc, 1,2Ali Sharifi-Zarchi, Ph.D, 2Nosratollah Zarghami, Ph.D, 1Lobat Geranpayeh, MD, 3Marzieh Ebrahimi, Ph.D., 2,*Effat Alizadeh, Ph.D., 4,*
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding Addresses: P.O. Box: 16635-148 Department of Stem Cells and Developmental Biology Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran P.O.Box: 5166653431 Drug Applied Research Center Tabriz University of Medical Sciences Tabriz Iran Emails:mebrahimi@royaninstitute.org,alizadehe@tbzmed.ac.ir
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Rahimi Mahsa, Sharifi-Zarchi Ali, Zarghami Nosratollah, Geranpayeh Lobat, Ebrahimi Marzieh, Alizadeh Effat. Down-Regulation of miR-200c and Up-Regulation of miR-30c Target both Stemness and Metastasis Genes in Breast Cancer . Cell J. 2020; 21(4): 467-478.

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.