miR-1 inhibits the proliferation of breast cancer stem cells by targeting EVI-1

• Published in: OncoTargets and therapy 2018-01, Vol.11, p.8773-8781
• Main Authors: Wu, Lei, Wang, Tianyi, He, Dongning, Li, Xiaoxi, Jiang, Youhong
• Format: Article
• Language: English
• Subjects: Apoptosis; Biotechnology; Breast cancer; Cancer research; Cancer therapies; Cancer treatment; Cell cycle; Cell growth; Flow cytometry; Fluorescein; Gastric cancer; Genes; Genetic research; Growth factors; Health aspects; Immunohistochemistry; Laboratories; Leukemia; Luciferase; Lung cancer; Medical prognosis; Messenger RNA; Metastasis; MicroRNA; MicroRNAs; Original Research; Patients; Stem cells; Tumors; Xenografts
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S188836

Breast cancer stem cells (BCSCs) have been regarded as the key factor for treatment failure in breast cancer. The abnormal expression of miRNAs plays a significant role in different tumor types. However, the role of miR-1 in breast cancer remains poorly understood. The purpose of this study was to evaluate the effects of miR-1 on the proliferation and apoptosis of BCSCs. CD44 /CD24 /epithelial-specific antigen BCSCs were isolated by flow cytometry. Real-time PCR and Western blotting were used to determine the expression of miRNAs, mRNAs, and epithelial-mesenchymal transition (EMT)-related genes. Cell proliferation and apoptosis were measured using the Cell Counting Kit-8 assay and Annexin V-fluorescein isothiocyanate flow cytometry, respectively. Luciferase reporter assay was used to verify whether miR-1 targeted ecotropic virus integration-1 (EVI-1). The role of miR-1 in breast cancer in vivo was evaluated using BCSCs xenograft mouse models. In this study, we demonstrated that miR-1 was significantly downregulated in breast cancer tissues compared to the adjacent non-tumor tissues. The luciferase reporter assay verified that EVI-1 was a direct target of miR-1, and upregulation of miR-1 negatively correlated with the expression of EVI-1 in BCSCs at both the transcriptional and posttranslational levels. Furthermore, overexpression of miR-1 inhibited BCSCs proliferation and promoted apoptosis, which was reversed by the overexpression of EVI-1. In addition, we demonstrated that aberrant expression of miR-1 could regulate EMT-related genes in BCSCs. Finally, immunohistochemical staining demonstrated that EVI-1 expression was decreased in BCSCs tumors following intra-tumoral miR-1 agomir treatment compared to the control group. miR-1 can negatively regulate the expression of EVI-1 and, thus, affect BCSCs proliferation, apoptosis, and EMT-related markers. Taken together, these findings demonstrate that miR-1 could be employed as a therapeutic strategy in the treatment of breast cancer.