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Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells

The known collaboration between all‐transretinoic acid and interferon motivates this study of the dependence of RA‐induced leukemic cell differentiation on interferon regulatory factor‐1 (IRF‐1), a transcription factor that is the main mediator of interferon effects. In the HL‐60 acute myeloid leuke...

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Autores principales: Zhu, Kaiyuan, Yue, Jianbo, Yen, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325585/
https://www.ncbi.nlm.nih.gov/pubmed/32617521
http://dx.doi.org/10.1096/fba.2020-00004
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author Zhu, Kaiyuan
Yue, Jianbo
Yen, Andrew
author_facet Zhu, Kaiyuan
Yue, Jianbo
Yen, Andrew
author_sort Zhu, Kaiyuan
collection PubMed
description The known collaboration between all‐transretinoic acid and interferon motivates this study of the dependence of RA‐induced leukemic cell differentiation on interferon regulatory factor‐1 (IRF‐1), a transcription factor that is the main mediator of interferon effects. In the HL‐60 acute myeloid leukemia (AML) model that represents a rare RA‐responsive subtype of AML, IRF‐1 is not expressed until RA induces its prominent expression, and ectopic IRF‐1 expression enhances RA‐induced differentiation, motivating interest in how IRF‐1 is putatively needed for RA response. Accordingly, we created CRISPR/Cas9‐mediated IRF‐1 knockout HL‐60 cells. Contrary to expectation, loss of IRF‐1 did not diminish RA‐induced cellular signaling that propels differentiation, and RA‐induced cell differentiation markers, including CD38 and CD11b expression and G1/G0cell cycle arrest, were unaffected. However, elimination of IRF‐1 inhibited RA‐induced p47phox expression and inducible oxidative metabolism detected by reactive oxygen species (ROS), suggesting IRF‐1 is essential for mature granulocytic inducible oxidative metabolism. In the case of 1,25‐Dihydroxyvitamin D3‐induced differentiation to monocytes, IRF‐1 loss did not affect D3‐induced expression of CD38, CD11b, and CD14, and G1/0 arrest; but inhibited ROS production. Our data suggest that IRF‐1 is inessential for differentiation but upregulates p47phox expression for mature‐cell ROS production.
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spelling pubmed-73255852020-07-01 Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells Zhu, Kaiyuan Yue, Jianbo Yen, Andrew FASEB Bioadv Research Article The known collaboration between all‐transretinoic acid and interferon motivates this study of the dependence of RA‐induced leukemic cell differentiation on interferon regulatory factor‐1 (IRF‐1), a transcription factor that is the main mediator of interferon effects. In the HL‐60 acute myeloid leukemia (AML) model that represents a rare RA‐responsive subtype of AML, IRF‐1 is not expressed until RA induces its prominent expression, and ectopic IRF‐1 expression enhances RA‐induced differentiation, motivating interest in how IRF‐1 is putatively needed for RA response. Accordingly, we created CRISPR/Cas9‐mediated IRF‐1 knockout HL‐60 cells. Contrary to expectation, loss of IRF‐1 did not diminish RA‐induced cellular signaling that propels differentiation, and RA‐induced cell differentiation markers, including CD38 and CD11b expression and G1/G0cell cycle arrest, were unaffected. However, elimination of IRF‐1 inhibited RA‐induced p47phox expression and inducible oxidative metabolism detected by reactive oxygen species (ROS), suggesting IRF‐1 is essential for mature granulocytic inducible oxidative metabolism. In the case of 1,25‐Dihydroxyvitamin D3‐induced differentiation to monocytes, IRF‐1 loss did not affect D3‐induced expression of CD38, CD11b, and CD14, and G1/0 arrest; but inhibited ROS production. Our data suggest that IRF‐1 is inessential for differentiation but upregulates p47phox expression for mature‐cell ROS production. John Wiley and Sons Inc. 2020-05-22 /pmc/articles/PMC7325585/ /pubmed/32617521 http://dx.doi.org/10.1096/fba.2020-00004 Text en © 2020 The Authors. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhu, Kaiyuan
Yue, Jianbo
Yen, Andrew
Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells
title Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells
title_full Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells
title_fullStr Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells
title_full_unstemmed Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells
title_short Depleting interferon regulatory factor‐1(IRF‐1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA‐induced differentiation in HL‐60 human AML cells
title_sort depleting interferon regulatory factor‐1(irf‐1) with crispr/cas9 attenuates inducible oxidative metabolism without affecting ra‐induced differentiation in hl‐60 human aml cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325585/
https://www.ncbi.nlm.nih.gov/pubmed/32617521
http://dx.doi.org/10.1096/fba.2020-00004
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