Downregulation of miR-205 contributes to epithelial–mesenchymal transition and invasion in triple-negative breast cancer by targeting HMGB1–RAGE signaling pathway

Our aim was to study the regulatory molecule networks involved in the epithelial-to-mesenchymal transition and thus promoting the early onset of metastasis in triple-negative breast cancer (TNBC). Forty pairs of human TNBC and their adjacent normal breast tissues were analyzed by real-time PCR and immunochemistry to demonstrate the correlation between the miR-205 expression and clinicopathological characteristics. In vitro, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, cell migration, and invasion assay were used to detect the cell growth and invasive ability of TNBC cells after upregulation or downregulation of miR-205 expression. Luciferase reporter assay was used to confirm the potential target directly influenced by miR-205. Our results showed that miR-205 abnormal expression may be involved and associated with the biological traits of TNBC. Ectopic expression of miR-205 not only inhibited cell growth, but also suppressed migration and invasion of mesenchymal-like TNBC cells. In addition, we found that overexpression of miR-205 significantly suppressed HMGB1 by binding its 3′-untranslated region, and that miR-205 was inversely correlated with the expression of HMGB1 and RAGE in cell lines and clinical samples. Our study illustrated that miR-205 was a tumor suppressor in TNBC, which attenuated the viability and the acquisition of the epithelial-to-mesenchymal transition phenotype TNBC cells at least partially exerted through targeting of HMGB1–RAGE signaling pathway. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://ift.tt/1hexVwJ * Ling Wang and Fu-biao Kang contributed equally to the writing of this article. Correspondence to Ling Wang, MD, PhD, Department of Orthopedic Oncology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, People's Republic of China Tel: +86 0311 8860 2590; fax: +86 0311 8860 3916; e-mail: wangling2016uw@126.com Received July 24, 2018 Accepted October 2, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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