Prdx2通过调节ROS-JNK1信号轴抑制红系分化
Prdx2 suppresses the erythroid differentiation by modulating the ROS-JNK1 signaling axis.
摘要(中文译文)
红白血病是急性髓系白血病中一种罕见但侵袭性强的亚型，预后差且治疗选择有限。红系分化受损是该病的标志性特征，但其潜在分子机制尚未被完全阐明。过氧化物还原酶2（PRDX2）是一种参与维持细胞氧化还原稳态的关键抗氧化酶，已在多种实体瘤中被提及，但其在红白血病发病机制中的作用尚未被探索。本研究采用单细胞RNA测序（scRNA-seq）对Friend鼠白血病病毒（F-MuLV）诱导的红白血病小鼠的骨髓微环境进行了分析。整合分析鉴定出PRDX2在多个恶性细胞群中显著上调。白血病骨髓中PRDX2表达升高伴随细胞内活性氧（ROS）水平降低，提示PRDX2介导的氧化还原调控与红白血病进展之间可能存在关联。在人红白血病细胞系K562和HEL中进行的功能实验表明，敲低PRDX2可抑制细胞积聚、增加细胞凋亡并促进红系分化。机制上，敲低PRDX2可升高ROS水平，而使用ROS抑制剂N-乙酰半胱氨酸（NAC）处理可逆转ROS升高和分化。此外，耗竭PRDX2选择性激活JNK1通路，而p38、ERK或mTOR信号未见变化。NAC处理可逆转JNK1激活，表明ROS通过JNK1调控分化。与此一致，使用JNK1抑制剂处理可逆转PRDX2敲低所诱导的分化，证实JNK1激活在功能上是必需的。总之，我们的研究结果确立了PRDX2作为红系分化阻滞的关键调控因子，并确定PRDX2是红白血病中基于分化的治疗的一个有前景的药理学可干预靶点。
Abstract
Erythroleukemia is a rare but aggressive subtype of acute myeloid leukemia with a poor prognosis and limited therapeutic options. Impaired erythroid differentiation is a hallmark of this disease, yet the underlying molecular mechanisms remain incompletely understood. Peroxiredoxin 2 (PRDX2), a key antioxidant enzyme involved in maintaining cellular redox homeostasis, has been implicated in various solid tumors, but its role in erythroleukemia pathogenesis has not been explored. In this study, we employed single-cell RNA sequencing (scRNA-seq) to profile the bone marrow microenvironment of Friend murine leukemia virus (F-MuLV)-induced erythroleukemia mice. Integrated analysis identified PRDX2 as a significantly upregulated molecule across multiple malignant cell populations. Elevated PRDX2 expression in leukemic bone marrow was accompanied by decreased intracellular reactive oxygen species (ROS) levels, suggesting a potential link between PRDX2-mediated redox regulation and erythroleukemia progression. Functional assays in human erythroleukemia cell lines K562 and HEL demonstrated that PRDX2 knockdown inhibited cell accumulation, increased apoptosis, and promoted erythroid differentiation. Mechanistically, PRDX2 knockdown elevated ROS levels, and treatment with the ROS inhibitor N-acetylcysteine (NAC) reversed both ROS elevation and differentiation. Furthermore, PRDX2 depletion selectively activated the JNK1 pathway, with no changes in p38, ERK, or mTOR signaling. NAC treatment reversed JNK1 activation, indicating that ROS modulates differentiation through JNK1. Consistently, treatment with a JNK1 inhibitor reversed the differentiation induced by PRDX2 knockdown, confirming that JNK1 activation is functionally required. Collectively, our findings establish PRDX2 as a critical regulator of erythroid differentiation blockade and identify PRDX2 as a promising pharmacologically actionable target for differentiation-based therapy in erythroleukemia.
如何引用
AMA
Dan Xie, Mingyue Yang, Sha Cheng, Bangquan An, Li Su, Fa Sun, et al. Prdx2 suppresses the erythroid differentiation by modulating the ROS-JNK1 signaling axis.. Biochimica et biophysica acta. Molecular basis of disease. 2027; doi:10.1016/j.bbadis.2026.168422.
APA
Dan Xie, Mingyue Yang, Sha Cheng, Bangquan An, Li Su, Fa Sun, et al (2027). Prdx2 suppresses the erythroid differentiation by modulating the ROS-JNK1 signaling axis.. Biochimica et biophysica acta. Molecular basis of disease. https://doi.org/10.1016/j.bbadis.2026.168422
GB/T 7714
Dan Xie, Mingyue Yang, Sha Cheng, Bangquan An, Li Su, Fa Sun, et al. Prdx2 suppresses the erythroid differentiation by modulating the ROS-JNK1 signaling axis.[J]. Biochimica et biophysica acta. Molecular basis of disease, 2027 doi:10.1016/j.bbadis.2026.168422.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出