Rahimi Mahsa, Sharifi-Zarchi Ali, Zarghami Nosratollah, Geranpayeh Lobat, Ebrahimi Marzieh, Alizadeh Effat
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.
Cell J. 2020 Jan;21(4):467-478. doi: 10.22074/cellj.2020.6406. Epub 2019 Jul 29.
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.
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.
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).
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.
微小RNA（miRNA）在肿瘤发生发展过程中发挥重要作用。它们可靶向肿瘤细胞尤其是癌症干细胞（CSC）的自我更新和上皮-间质转化（EMT）能力。本研究的目的是通过数据挖掘来识别靶向自我更新和EMT的重要miRNA。我们还旨在评估这些因子在作为乳腺癌干细胞（BCSC）模型的乳腺球和转移性肿瘤组织中的情况。
在本实验研究中，从MCF-7细胞中获得乳腺球并对其CSC特性进行表征。然后，使用从7名患者获得的乳腺肿瘤细胞评估所选miRNA在球体中的表达模式。在乳腺球和转移性肿瘤中评估miRNA与自我更新和EMT候选基因的相关性。
结果表明，乳腺球比MCF-7细胞具有更强的集落形成和球体形成潜力（P<0.05）。此外，它们具有增强的迁移和侵袭能力。我们的计算分析确定，[具体miRNA名称1]和[具体miRNA名称2]可能是靶向干性和EMT途径的候选者。[具体miRNA名称1]的表达水平降低，而[具体miRNA名称2]在乳腺球中的表达水平升高，这与从3名接受新辅助治疗的II/III级患者分离的乳腺肿瘤组织相似。假定的干细胞标志物（[具体标志物名称1]）和EMT相关基因（[具体基因名称1]）的表达水平在乳腺球和3名指定患者中也显著增加（P<0.05）。
新辅助治疗后患者中，[具体miRNA名称1]下调和[具体miRNA名称2]上调可能是BCSC富集的特征。因此，靶向[具体miRNA名称1]和[具体miRNA名称2]可能有助于开发针对BCSC的新治疗方法。
