Chidamide induces cell cycle arrest via NR4A3/P21 axis upregulation to suppress relapsed and refractory acute myeloid leukemia.

Autor: Feng X; Department of Hematology, Key Laboratory of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China., Luo F; Department of Graduate School, Hebei North University, 075000, Zhangjiakou, Hebei, China., Wang S; Department of Graduate School, Hebei North University, 075000, Zhangjiakou, Hebei, China., Zhu F; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China., Gao Y; Department of Hematology, Key Laboratory of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China., Luo J; Department of Hematology, Key Laboratory of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. Electronic address: luojianmin1960@126.com., Zhou J; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: zhoujiazi@suda.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 10; Vol. 737, pp. 150493. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1016/j.bbrc.2024.150493
Abstrakt: (1) Currently, the survival prognosis for patients with relapsed and refractory acute myeloid leukemia (R/R AML) is extremely poor. Therefore, the exploration of novel drugs is imperative to enhance the prognosis of patients with R/R AML. The therapeutic efficacy and mechanism of Chidamide, a novel epigenetic regulatory drug, in the treatment of R/R AML remain unclear.
Methods: The mechanism of action of Chidamide has been explored in various AML cell lines through various methods such as cell apoptosis, cell cycle analysis, high-throughput transcriptome sequencing, gene silencing, and xenograft models.
Results: Here, we have discovered that chidamide potently induces apoptosis, G0/G1 phase arrest, and mitochondrial membrane potential depolarization in R/R AML cells, encompassing both primary cells and cell lines. Through RNA-seq analysis, we further revealed that chidamide epigenetically regulates the upregulation of differentiation-related pathways while suppressing those associated with cell replication and cell cycle progression. Notably, our screening identified NR4A3 as a key suppressor gene whose upregulation by chidamide leads to P21-dependent cell cycle arrest in the G0/G1 phase.
Conclusions: We have discovered a novel epigenetic regulatory mechanism of chidamide in the treatment of relapsed and refractory acute myeloid leukemia (R/R AML).
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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