FOXP3 and miR-155 cooperate to control the invasive potential of human breast cancer cells by down regulating ZEB2 independently of ZEB1.

Autor:	Brown CY; Discipline of Paediatrics, School of Medicine, Women's and Children's Hospital, University of Adelaide, Adelaide, 5006 SA, Australia.; Molecular Immunology, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia., Dayan S; Molecular Immunology, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia.; Department of Gastroenterology, WCHN, Adelaide, 5006 SA, Australia., Wong SW; Molecular Immunology, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia., Kaczmarek A; Research Centre for Reproductive Health, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia., Hope CM; Discipline of Paediatrics, School of Medicine, Women's and Children's Hospital, University of Adelaide, Adelaide, 5006 SA, Australia., Pederson SM; Molecular Immunology, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia., Arnet V; Gene Regulation Laboratory, Centre for Cancer Biology, University of South Australia, Adelaide, 5006 SA, Australia., Goodall GJ; Gene Regulation Laboratory, Centre for Cancer Biology, University of South Australia, Adelaide, 5006 SA, Australia., Russell D; Research Centre for Reproductive Health, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia., Sadlon TJ; Molecular Immunology, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia.; Department of Gastroenterology, WCHN, Adelaide, 5006 SA, Australia., Barry SC; Discipline of Paediatrics, School of Medicine, Women's and Children's Hospital, University of Adelaide, Adelaide, 5006 SA, Australia.; Molecular Immunology, Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, 5005 SA, Australia.; Department of Gastroenterology, WCHN, Adelaide, 5006 SA, Australia.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Jun 12; Vol. 9 (45), pp. 27708-27727. Date of Electronic Publication: 2018 Jun 12 (Print Publication: 2018).
DOI:	10.18632/oncotarget.25523
Abstrakt:	Control of oncogenes, including ZEB1 and ZEB2, is a major checkpoint for preventing cancer, and loss of this control contributes to many cancers, including breast cancer. Thus tumour suppressors, such as FOXP3, which is mutated or lost in many cancer tissues, play an important role in maintaining normal tissue homeostasis. Here we show for the first time that ZEB2 is selectively down regulated by FOXP3 and also by the FOXP3 induced microRNA, miR-155. Interestingly, neither FOXP3 nor miR-155 directly altered the expression of ZEB1. In breast cancer cells repression of ZEB2, independently of ZEB1, resulted in reduced expression of a mesenchymal marker, Vimentin and reduced invasion. However, there was no de-repression of E-cadherin and migration was enhanced. Small interfering RNAs targeting ZEB2 suggest that this was a direct effect of ZEB2 and not FOXP3/miR-155. In normal human mammary epithelial cells, depletion of endogenous FOXP3 resulted in de-repression of ZEB2, accompanied by upregulated expression of vimentin, increased E-cadherin expression and cell morphological changes. We suggest that FOXP3 may help maintain normal breast epithelial characteristics through regulation of ZEB2, and loss of FOXP3 in breast cancer cells results in deregulation of ZEB2. Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu