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

Authors Wu L, Wang T, He D, Li X, Jiang Y

Received 26 September 2018

Accepted for publication 3 November 2018

Published 6 December 2018 Volume 2018:11 Pages 8773—8781

DOI https://doi.org/10.2147/OTT.S188836

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava


Lei Wu,1 Tianyi Wang,2 Dongning He,2 Xiaoxi Li,1 Youhong Jiang1

1Molecular Oncology Laboratory of Cancer Research Institute, The First Hospital of China Medical University, Shenyang 110001, China; 2Department of Medical Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China

Purpose: 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.
Materials and methods: CD44+/CD24-/low/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.
Results: 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 intratumoral miR-1 agomir treatment compared to the control group.
Conclusion: 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.

Keywords: breast cancer, miR-1, proliferation, apoptosis, EVI-1

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