Decreasing of serine/threonine kinase 39 has tumour inhibiting effects on acute myeloid leukaemia by impacting the PI3K/AKT and Wnt/β-catenin signalling cascades

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2024-05-29 DOI:10.1016/j.taap.2024.116982

Chengliang Li , Hong Xin , Jiajia Hao , Yudi Miao

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Abstract

Serine/threonine kinase 39 (STK39) has been identified as a key regulator of tumour progression. However, whether STK39 plays a role in acute myeloid leukaemia (AML) remains undetermined. This work explored the expression and functions of STK39 in AML. STK39 was found to be overexpressed in AML and was negatively correlated with overall survival. Functionally, silencing STK39 inhibited cell proliferation, promoted cell differentiation and induced cell cycle arrest and apoptosis. The tumour inhibiting effects of STK39 downregulation were also verified by an in vivo xenograft tumour assay. Mechanistically, STK39 was closely related to the PI3K/AKT and Wnt/β-catenin signalling cascades in AML. Silencing of STK39 had suppressive effects on the PI3K/AKT and Wnt/β-catenin signalling cascades. The suppressive effect of STK39 silencing on the Wnt/β-catenin signalling cascade was significantly reversed when PI3K/AKT was reactivated. When β-catenin was re-expressed, the tumour-inhibiting effects caused by STK39 silencing were significantly eliminated. Therefore, STK39 plays a crucial role in AML and could be targeted for potential therapeutic purposes in treating AML.

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通过影响 PI3K/AKT 和 Wnt/β-catenin 信号级联，减少丝氨酸/苏氨酸激酶 39 对急性髓性白血病有抑制肿瘤的作用。

丝氨酸/苏氨酸激酶 39（STK39）已被确定为肿瘤进展的关键调节因子。然而，STK39是否在急性髓性白血病（AML）中发挥作用仍未确定。这项研究探讨了 STK39 在急性髓性白血病中的表达和功能。研究发现，STK39在急性髓性白血病中过表达，并与总生存率呈负相关。在功能上，沉默STK39可抑制细胞增殖、促进细胞分化、诱导细胞周期停滞和细胞凋亡。体内异种移植肿瘤实验也验证了下调STK39对肿瘤的抑制作用。从机理上讲，STK39与AML中的PI3K/AKT和Wnt/β-catenin信号级联密切相关。沉默STK39对PI3K/AKT和Wnt/β-catenin信号级联有抑制作用。当PI3K/AKT被重新激活时，沉默STK39对Wnt/β-catenin信号级联的抑制作用被明显逆转。当β-catenin重新表达时，STK39沉默引起的肿瘤抑制作用明显消失。因此，STK39在急性髓细胞性白血病中起着关键作用，可作为治疗急性髓细胞性白血病的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.