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miR-26b-5p 通过调控 USP48 介导的 Wnt/β-连环蛋白通路影响急性髓系白血病的进展。

miR-26b-5p Affects the Progression of Acute Myeloid Leukemia by Regulating the USP48-Mediated Wnt/β-Catenin Pathway.

机构信息

Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

出版信息

Crit Rev Eukaryot Gene Expr. 2024;34(4):33-44. doi: 10.1615/CritRevEukaryotGeneExpr.2024049380.

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous disease. Exploring the pathogenesis of AML is still an important topic in the treatment of AML. The expression levels of miR-26b-5p and USP48 were measured by qRT-PCR. The expression levels of related proteins were detected by Western blot. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. Coimmunoprecipitation was used to examine the interaction between USP48 and Wnt5a. Bioinformatics analysis showed that high levels of miR-26b-5p and low levels of USP48 were associated with poor prognosis in AML. miR-26b-5p can negatively regulate the expression of USP48. Downregulation of miR-26b-5p inhibited EMT, cell viability and proliferation of AML cells and accelerated apoptosis. Furthermore, the influence of miR-26b-5p inhibition and USP48 knockdown on AML progression could be reversed by a Wnt/β-catenin signaling pathway inhibitor. This study revealed that miR-26b-5p regulates AML progression, possibly by targeting the USP48-mediated Wnt/β-catenin molecular axis to affect AML cell biological behavior.

摘要

急性髓系白血病(AML)是一种高度异质性疾病。探索 AML 的发病机制仍然是 AML 治疗中的一个重要课题。采用 qRT-PCR 检测 miR-26b-5p 和 USP48 的表达水平。采用 Western blot 检测相关蛋白的表达水平。分别采用 CCK-8 和流式细胞术检测细胞增殖和凋亡。采用 co-immunoprecipitation 检测 USP48 和 Wnt5a 之间的相互作用。生物信息学分析显示,miR-26b-5p 高表达和 USP48 低表达与 AML 的不良预后相关。miR-26b-5p 可以负调控 USP48 的表达。下调 miR-26b-5p 抑制 AML 细胞的 EMT、细胞活力和增殖,并加速细胞凋亡。此外,Wnt/β-catenin 信号通路抑制剂可逆转 miR-26b-5p 抑制和 USP48 敲低对 AML 进展的影响。本研究表明,miR-26b-5p 通过靶向 USP48 介导的 Wnt/β-catenin 分子轴来调节 AML 的进展,从而影响 AML 细胞的生物学行为。

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