Hongyan Zhang, Liang Zhong, Meng Wang, Peng Wan, Xuan Chu, Shuyu Chen, Ziwei Zhou, Xin Shao, Beizhong Liu
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引用次数: 0
摘要
作为一种进化保守的转录因子,类切割同源染色体 1(CUT-like homeobox 1,CUX1)在胚胎和神经系统发育、细胞分化以及 DNA 损伤修复中发挥着至关重要的作用。其主要异构体之一 p110CUX1 具有稳定的 DNA 结合能力,有助于调节细胞周期的进展、增殖、迁移和侵袭。虽然 p110CUX1 与各种恶性肿瘤的进展有牵连,但它在急性髓性白血病(AML)中的参与情况仍不确定。本研究旨在阐明 p110CUX1 在急性髓性白血病中的作用。我们的研究结果表明,p110CUX1 和吡哆醛磷酸酶(PDXP)在急性髓性白血病细胞系中的表达水平都有所提高。过表达 p110CUX1 会促进 AML 细胞增殖,同时抑制细胞凋亡和分化,而敲除 PDXP 则会产生相反的效果。从机理上讲,p110CUX1 似乎通过上调 PDXP 的表达和激活 PI3K/AKT/mTOR 信号通路来促进急性髓细胞性白血病的发展。动物实验证实了 p110CUX1 对急性髓细胞性白血病的促进作用。这些结果为p110CUX1-PDXP-PI3K/AKT/mTOR轴参与AML进展提供了实验证据。因此,以 p110CUX1 为靶点可能有望成为治疗急性髓细胞性白血病的一种策略。
p110CUX1 promotes acute myeloid leukemia progression via regulating pyridoxal phosphatase expression and activating PI3K/AKT/mTOR signaling pathway.
As an evolutionarily conserved transcription factor, Cut-like homeobox 1 (CUX1) plays crucial roles in embryonic and nervous system development, cell differentiation, and DNA damage repair. One of its major isoforms, p110CUX1, exhibits stable DNA binding capabilities and contributes to the regulation of cell cycle progression, proliferation, migration, and invasion. While p110CUX1 has been implicated in the progression of various malignant tumors, its involvement in acute myeloid leukemia (AML) remains uncertain. This study aims to elucidate the role of p110CUX1 in AML. Our findings reveal heightened expression levels of both p110CUX1 and pyridoxal phosphatase (PDXP) in AML cell lines. Overexpression of p110CUX1 promotes AML cell proliferation while inhibiting apoptosis and differentiation, whereas knockdown of PDXP yields contrasting effects. Mechanistically, p110CUX1 appears to facilitate AML development by upregulating PDXP expression and activating the PI3K/AKT/mTOR signaling pathway. Animal experimental corroborate the pro-AML effect of p110CUX1. These results provide experimental evidence supporting the involvement of the p110CUX1-PDXP-PI3K/AKT/mTOR axis in AML progression. Hence, targeting p110CUX1 may hold promise as a therapeutic strategy for AML.
期刊介绍:
Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.