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NONO 对 SAMHD1 的稳定作用对 AML 中阿糖胞苷耐药至关重要。

Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML.

机构信息

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Central Laboratory, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, North 128 Xiangshan Road, Nanchang, 330008, China.

College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.

出版信息

Cell Death Dis. 2022 Jul 8;13(7):590. doi: 10.1038/s41419-022-05023-0.

DOI:10.1038/s41419-022-05023-0
PMID:35803902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9270467/
Abstract

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.

摘要

阿糖胞苷（Ara-C）是治疗急性髓细胞白血病（AML）的一线药物。然而，最终会产生耐药性，降低 AML 患者使用 Ara-C 的疗效。脱氧核苷三磷酸（dNTP）三磷酸水解酶 SAMHD1 的表达在 Ara-C 耐药的 AML 患者中升高，并在介导 AML 中的 Ara-C 耐药中发挥关键作用。然而，SAMHD1 在耐药 AML 中上调的机制尚不清楚。在这项研究中，NONO 通过抑制 DCAF1 介导的 SAMHD1 的泛素化/降解来与 SAMHD1 相互作用并稳定其。NONO 的过表达增加了 SAMHD1 的表达并降低了 AML 细胞对 Ara-C 的敏感性，而下调 NONO 则产生相反的效果。此外，DNA 损伤剂顺铂（DDP）和阿霉素（ADM）降低了 NONO/SAMHD1 的表达并使 AML 细胞对 Ara-C 敏感。更重要的是，Ara-C 耐药的 AML 细胞中 NONO 上调，导致耐药 AML 细胞中 SAMHD1 的表达增加，DDP 和 ADM 治疗使耐药 AML 细胞对 Ara-C 重新敏感。本研究揭示了 Ara-C 耐药的 AML 细胞中 SAMHD1 上调的机制，并为 Ara-C 耐药的 AML 提供了新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/3e795dee0365/41419_2022_5023_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/b9013741d1a0/41419_2022_5023_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/b5befe462fb9/41419_2022_5023_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/81ad4a68a284/41419_2022_5023_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/733c5b1111ec/41419_2022_5023_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/ff787ba0a1d4/41419_2022_5023_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/c482066d40f2/41419_2022_5023_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/06aed3546e01/41419_2022_5023_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/3e795dee0365/41419_2022_5023_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/b9013741d1a0/41419_2022_5023_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/b5befe462fb9/41419_2022_5023_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/81ad4a68a284/41419_2022_5023_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/733c5b1111ec/41419_2022_5023_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/ff787ba0a1d4/41419_2022_5023_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/c482066d40f2/41419_2022_5023_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/06aed3546e01/41419_2022_5023_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e14/9270467/3e795dee0365/41419_2022_5023_Fig8_HTML.jpg

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EBioMedicine. 2021 Jul;69:103441. doi: 10.1016/j.ebiom.2021.103441. Epub 2021 Jun 21.
3
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Indian J Hematol Blood Transfus. 2024 Oct;40(4):629-637. doi: 10.1007/s12288-024-01773-3. Epub 2024 May 27.
4
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Discov Oncol. 2024 Jun 11;15(1):221. doi: 10.1007/s12672-024-01072-3.
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