miR-200a inhibits migration of triple-negative breast cancer cells through direct repression of the EPHA2 oncogene

Efrosini Tsouko, Jun Wang, Daniel E. Frigo, Eylem Aydogdu, Cecilia Williams

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Triple-negative breast cancer (TNBC) is characterized by aggressiveness and affects 10-20% of breast cancer patients. Since TNBC lacks expression of ERa, PR and HER2, existing targeted treatments are not effective and the survival is poor. In this study, we demonstrate that the tumor suppressor microRNA miR-200a directly regulates the oncogene EPH receptor A2 (EPHA2) and modulates TNBC migration. We show that EPHA2 expression is correlated with poor survival specifically in basal-like breast cancer and that its expression is repressed by miR-200a through direct interaction with the 3'UTR of EPHA2. This regulation subsequently affects the downstream activation of AMP-activated protein kinase (AMPK) and results in decreased cell migration of TNBC. We establish that miR-200a directs cell migration in a dual manner; in addition to regulating the well-characterized E-cadherin pathway it also regulates a EPHA2 pathway. The miR-200a-EPHA2 axis is a novel mechanism highlighting the possibility of utilizing miR-200a delivery to target TNBC metastases.

Original languageEnglish (US)
Pages (from-to)1051-1060
Number of pages10
JournalCarcinogenesis
Volume36
Issue number9
DOIs
StatePublished - Mar 24 2015

ASJC Scopus subject areas

  • Cancer Research

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