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

作者：Lin, Chenghui; Gao, Bin; Yang, Xuemao; Lei, Zixiong; Chen, Kebing; Li, Yuquan; Zeng, Qing; Chen, Zeqin; Li, Haomiao^*

来源：OncoTargets and Therapy, 2018, 11: 5419-5428.

DOI：10.2147/OTT.S164575

• breast cancer stem cells
• CD44(+)/CD24(-)
• miR-628
• SOS1
• migration
• invasion

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.

• 出版日期2018
• 单位南方医科大学