Annexin A2 binds the 3′-UTR of H2AX mRNA and regulates histone-H2AX-derived hypoxia-inducible factor 1-alpha activation

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-03-29 DOI:10.1016/j.cellsig.2025.111781

Shiyin Zhang , Yu-Shi Wang , Yang Li , Kwang-Il To , En-Ting Zhang , Ying-Hua Jin

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引用次数: 0

Abstract

Annexin A2 (Anxa2), a multifunctional protein with RNA-binding capabilities, is frequently overexpressed in various tumors, and its expression is highly correlated with malignant progression. In this study, we demonstrate for the first time that Anxa2 was co-expressed with glycolytic genes, suggesting its potential role as a regulator of glycolysis. RNA-protein interaction assay revealed that Anxa2 interacted with 3′-UTR of H2AX mRNA and protected it from miRNA-mediated degradation. Up-regulated Histone-H2AX enhances the expression of glycolytic genes including GLUT1, HK2, PGK1, ENO1, PKM2, GAPDH and LDHA via stabilizing hypoxia-inducible factor 1-alpha (HIF1α), thereby accelerating lactic acid production and secretion. (20S) G-Rh2, a natural compound targeting Anxa2, significantly interfered the Anxa2-H2AX mRNA interaction, and inhibited subsequent glycolysis progression. We propose that Anxa2 acts as a novel regulator in glycolysis via enhancing H2AX expression, and (20S) G-Rh2 may exert its anti-cancer activity by targeting Anxa2-H2AX-HIF1α-glycolysis axis in human hepatoma HepG2 cells.

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Annexin A2结合H2AX mRNA的3'-UTR，调节组蛋白H2AX衍生的缺氧诱导因子1- α的激活。

膜联蛋白A2 （Anxa2）是一种具有rna结合能力的多功能蛋白，在各种肿瘤中经常过表达，其表达与恶性进展高度相关。在这项研究中，我们首次证明了Anxa2与糖酵解基因共表达，表明其作为糖酵解调节因子的潜在作用。rna -蛋白相互作用实验显示，Anxa2与H2AX mRNA的3′-UTR相互作用，保护H2AX mRNA免受mirna介导的降解。上调组蛋白- h2ax通过稳定缺氧诱导因子1- α (HIF1α)，增强糖酵解基因GLUT1、HK2、PGK1、ENO1、PKM2、GAPDH和LDHA的表达，从而加速乳酸的产生和分泌。（20S） G-Rh2是一种靶向Anxa2的天然化合物，显著干扰了Anxa2- h2ax mRNA的相互作用，并抑制了随后的糖酵解进程。我们认为Anxa2通过增强H2AX的表达而在糖酵解中发挥新的调节作用，并且（20S） G-Rh2可能通过靶向人肝癌HepG2细胞中的Anxa2-H2AX- hif1 α-糖酵解轴发挥其抗癌活性。

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

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.