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

Abstract

PurposeThe 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 methodsQuantitative 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.ResultsCompared 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.ConclusionmiR-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.