title: miR-200a inhibits migration of triple-negative breast cancer cells through direct repression of the EPHA2 oncogene.
abstract: Triple-negative breast cancer (TNBC) is characterized by aggressiveness and affects 10-20% of breast cancer patients. Since TNBC lacks expression of ERα, 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.
authors.affiliation: Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3605 Cullen Blvd., Houston, TX 77204, USA.
authors.forename: Efrosini
authors.initials: E
authors.lastname: Tsouko
authors.affiliation: Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3605 Cullen Blvd., Houston, TX 77204, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3605 Cullen Blvd., Houston, TX 77204, USA, Genomic Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA and.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Frigo
authors.affiliation: Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3605 Cullen Blvd., Houston, TX 77204, USA, Present address: Department of Plant Systems Biology, VIB, Ghent, Belgium.
authors.forename: Eylem
authors.initials: E
authors.lastname: Aydoğdu
authors.affiliation: Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3605 Cullen Blvd., Houston, TX 77204, USA, Science for Life Laboratory, School of Biotechnology, KTH - Royal Institute of Technology, 171 21 Stockholm, Sweden cecilia.williams@scilifelab.se.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Williams
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D036104:Receptor, EphA2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D036104:Receptor, EphA2; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase