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miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3

MicroRNAs (miRNAs) are emerging as critical regulators of normal and malignant hematopoiesis. In previous studies of acute myeloid leukemia miR-9 overexpression was commonly observed. Here, we show that ectopic expression of miR-9 in vitro and in vivo significantly blocks differentiation of erythroi...

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Autores principales: Zhang, Yunyuan, Li, Liping, Yu, Chunjie, Senyuk, Vitalyi, Li, Fuxing, Quigley, John G., Zhu, Tongyu, Qian, Zhijian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916915/
https://www.ncbi.nlm.nih.gov/pubmed/29695725
http://dx.doi.org/10.1038/s41598-018-24628-0
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author Zhang, Yunyuan
Li, Liping
Yu, Chunjie
Senyuk, Vitalyi
Li, Fuxing
Quigley, John G.
Zhu, Tongyu
Qian, Zhijian
author_facet Zhang, Yunyuan
Li, Liping
Yu, Chunjie
Senyuk, Vitalyi
Li, Fuxing
Quigley, John G.
Zhu, Tongyu
Qian, Zhijian
author_sort Zhang, Yunyuan
collection PubMed
description MicroRNAs (miRNAs) are emerging as critical regulators of normal and malignant hematopoiesis. In previous studies of acute myeloid leukemia miR-9 overexpression was commonly observed. Here, we show that ectopic expression of miR-9 in vitro and in vivo significantly blocks differentiation of erythroid progenitor cells with an increase in reactive oxygen species (ROS) production. Consistent with this observation, ROS scavenging enzymes, including superoxide dismutase (Sod2), Catalase (Cat), and glutathine peroxidase (Gpx1), are down-regulated by miR-9. In addition, miR-9 suppresses expression of the erythroid transcriptional regulator FoxO3, and its down-stream targets Btg1 and Cited 2 in erythroid progenitor cells, while expression of a constitutively active form of FoxO3 (FoxO3-3A) reverses miR-9-induced suppression of erythroid differentiation, and inhibits miR-9-induced ROS production. Thus, our findings indicate that aberrant expression of miR-9 blocks erythropoiesis by deregulating FoxO3-mediated pathways, which may contribute to the ineffective erythropoiesis observed in patients with hematological malignancies.
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spelling pubmed-59169152018-04-30 miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3 Zhang, Yunyuan Li, Liping Yu, Chunjie Senyuk, Vitalyi Li, Fuxing Quigley, John G. Zhu, Tongyu Qian, Zhijian Sci Rep Article MicroRNAs (miRNAs) are emerging as critical regulators of normal and malignant hematopoiesis. In previous studies of acute myeloid leukemia miR-9 overexpression was commonly observed. Here, we show that ectopic expression of miR-9 in vitro and in vivo significantly blocks differentiation of erythroid progenitor cells with an increase in reactive oxygen species (ROS) production. Consistent with this observation, ROS scavenging enzymes, including superoxide dismutase (Sod2), Catalase (Cat), and glutathine peroxidase (Gpx1), are down-regulated by miR-9. In addition, miR-9 suppresses expression of the erythroid transcriptional regulator FoxO3, and its down-stream targets Btg1 and Cited 2 in erythroid progenitor cells, while expression of a constitutively active form of FoxO3 (FoxO3-3A) reverses miR-9-induced suppression of erythroid differentiation, and inhibits miR-9-induced ROS production. Thus, our findings indicate that aberrant expression of miR-9 blocks erythropoiesis by deregulating FoxO3-mediated pathways, which may contribute to the ineffective erythropoiesis observed in patients with hematological malignancies. Nature Publishing Group UK 2018-04-25 /pmc/articles/PMC5916915/ /pubmed/29695725 http://dx.doi.org/10.1038/s41598-018-24628-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Yunyuan
Li, Liping
Yu, Chunjie
Senyuk, Vitalyi
Li, Fuxing
Quigley, John G.
Zhu, Tongyu
Qian, Zhijian
miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3
title miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3
title_full miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3
title_fullStr miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3
title_full_unstemmed miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3
title_short miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3
title_sort mir-9 upregulation leads to inhibition of erythropoiesis by repressing foxo3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916915/
https://www.ncbi.nlm.nih.gov/pubmed/29695725
http://dx.doi.org/10.1038/s41598-018-24628-0
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