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Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML
Cytarabine (Ara-C) is the first-line drug for the treatment of acute myelogenous leukemia (AML). However, resistance eventually develops, decreasing the efficacy of Ara-C in AML patients. The expression of SAMHD1, a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, has been reported to be ele...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270467/ https://www.ncbi.nlm.nih.gov/pubmed/35803902 http://dx.doi.org/10.1038/s41419-022-05023-0 |
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author | Zhang, Feifei Sun, Jun Tang, Xiaofeng Liang, Yiping Jiao, Quanhui Yu, Bo Dai, Zhengzai Yuan, Xuhui Li, Jiayu Yan, Jinhua Zhang, Zhiping Fan, Song Wang, Min Hu, Haiyan Zhang, Changhua Lv, Xiao-Bin |
author_facet | Zhang, Feifei Sun, Jun Tang, Xiaofeng Liang, Yiping Jiao, Quanhui Yu, Bo Dai, Zhengzai Yuan, Xuhui Li, Jiayu Yan, Jinhua Zhang, Zhiping Fan, Song Wang, Min Hu, Haiyan Zhang, Changhua Lv, Xiao-Bin |
author_sort | Zhang, Feifei |
collection | PubMed |
description | Cytarabine (Ara-C) is the first-line drug for the treatment of acute myelogenous leukemia (AML). However, resistance eventually develops, decreasing the efficacy of Ara-C in AML patients. The expression of SAMHD1, a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, has been reported to be elevated in Ara-C-resistant AML patients and to play a crucial role in mediating Ara-C resistance in AML. However, the mechanism by which SAMHD1 is upregulated in resistant AML remains unknown. In this study, NONO interacted with and stabilized SAMHD1 by inhibiting DCAF1-mediated ubiquitination/degradation of SAMHD1. Overexpression of NONO increased SAMHD1 expression and reduced the sensitivity of AML cells to Ara-C, and downregulation of NONO had the opposite effects. In addition, the DNA-damaging agents DDP and adriamycin (ADM) reduced NONO/SAMHD1 expression and sensitized AML cells to Ara-C. More importantly, NONO was upregulated in Ara-C-resistant AML cells, resulting in increased SAMHD1 expression in resistant AML cells, and DDP and ADM treatment resensitized resistant AML cells to Ara-C. This study revealed the mechanism by which SAMHD1 is upregulated in Ara-C-resistant AML cells and provided novel therapeutic strategies for Ara-C-resistant AML. |
format | Online Article Text |
id | pubmed-9270467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92704672022-07-10 Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML Zhang, Feifei Sun, Jun Tang, Xiaofeng Liang, Yiping Jiao, Quanhui Yu, Bo Dai, Zhengzai Yuan, Xuhui Li, Jiayu Yan, Jinhua Zhang, Zhiping Fan, Song Wang, Min Hu, Haiyan Zhang, Changhua Lv, Xiao-Bin Cell Death Dis Article Cytarabine (Ara-C) is the first-line drug for the treatment of acute myelogenous leukemia (AML). However, resistance eventually develops, decreasing the efficacy of Ara-C in AML patients. The expression of SAMHD1, a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, has been reported to be elevated in Ara-C-resistant AML patients and to play a crucial role in mediating Ara-C resistance in AML. However, the mechanism by which SAMHD1 is upregulated in resistant AML remains unknown. In this study, NONO interacted with and stabilized SAMHD1 by inhibiting DCAF1-mediated ubiquitination/degradation of SAMHD1. Overexpression of NONO increased SAMHD1 expression and reduced the sensitivity of AML cells to Ara-C, and downregulation of NONO had the opposite effects. In addition, the DNA-damaging agents DDP and adriamycin (ADM) reduced NONO/SAMHD1 expression and sensitized AML cells to Ara-C. More importantly, NONO was upregulated in Ara-C-resistant AML cells, resulting in increased SAMHD1 expression in resistant AML cells, and DDP and ADM treatment resensitized resistant AML cells to Ara-C. This study revealed the mechanism by which SAMHD1 is upregulated in Ara-C-resistant AML cells and provided novel therapeutic strategies for Ara-C-resistant AML. Nature Publishing Group UK 2022-07-08 /pmc/articles/PMC9270467/ /pubmed/35803902 http://dx.doi.org/10.1038/s41419-022-05023-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Feifei Sun, Jun Tang, Xiaofeng Liang, Yiping Jiao, Quanhui Yu, Bo Dai, Zhengzai Yuan, Xuhui Li, Jiayu Yan, Jinhua Zhang, Zhiping Fan, Song Wang, Min Hu, Haiyan Zhang, Changhua Lv, Xiao-Bin Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML |
title | Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML |
title_full | Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML |
title_fullStr | Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML |
title_full_unstemmed | Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML |
title_short | Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML |
title_sort | stabilization of samhd1 by nono is crucial for ara-c resistance in aml |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270467/ https://www.ncbi.nlm.nih.gov/pubmed/35803902 http://dx.doi.org/10.1038/s41419-022-05023-0 |
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