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MicroRNA 628 suppresses migration and invasion of breast cancer stem cells through targeting SOS1

Authors Lin C, Gao B, Yan X, Lei Z, Chen K, Li Y, Zeng Q, Chen Z, Li H

Received 4 February 2018

Accepted for publication 30 May 2018

Published 4 September 2018 Volume 2018:11 Pages 5419—5428

DOI https://doi.org/10.2147/OTT.S164575

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Jianmin Xu


Chenghui Lin,1,* Bin Gao,2,* Xuemao Yan,2 Zixiong Lei,3 Kebing Chen,3 Yuquan Li,2 Qing Zeng,2 Zeqin Chen,2 Haomiao Li3

1Department of Medical oncology, TangXia Hospital of DongGuan, DongGuan, P.R. China; 2Department of Orthopedics, TangXia Hospital of DongGuan, DongGuan, P.R. China; 3Department of Musculoskeletal Oncology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, P.R. China

*These authors contributed equally to this work

Purpose: The purpose of this study is to evaluate the effects of miR-628 on migration and invasion of breast cancer stem cells (CSCs), which are essential for tumor recurrence and metastasis.
Materials and methods: Quantitative reverse transcription-polymerase chain reaction was used to determine the expression of microRNAs and mRNAs. A subpopulation of CD44+/CD24- breast CSCs were sorted by flow cytometry. Transwell assays were used to evaluate cell migration and invasion. Luciferase reporter assays were performed to verify whether miR-628 targeted SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1). pcDNA3.1(+)-SOS1 was constructed for overexpressing SOS1 after transfection.
Results: Compared with primary breast cancer cells, bone metastatic breast cancer cells showed significant downregulation of miR-628. The CD44+/CD24- breast CSC subpopulations in MDA-MB-231 and MCF-7 cell lines were analyzed and sorted. Transfection with an miR-628 mimic significantly suppressed the migration and invasion of these breast CSCs by targeting SOS1, which plays an essential role in epithelial-to-mesenchymal transition. Overexpression of SOS1 rescued miR-628-mediated migration and invasion by upregulating Snail and vimentin, and downregulating E-cadherin.
Conclusion: miR-628 suppressed migration and invasion of breast CSCs of MDA-MB-231 and MCF-7 cells by directly targeting SOS1. Enhancement of miR-628 expression might be an effective strategy for managing breast cancer metastasis.

Keywords:
breast cancer stem cells, CD44+/CD24-, miR-628, SOS1, migration, invasion

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