RNA-Binding Protein DHX9 Enhances Radioresistance in Metastatic Hepatocellular Carcinoma by Activation of the PI3K/Akt Pathway Through Enhanced EEF1A2 mRNA Stability

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-16 DOI:10.1002/jbt.70356

HaiBo Wang, Wei Cui

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Abstract

This study elucidated the role of Eukaryotic Elongation Factor 1 Alpha 2 (EEF1A2) and RNA-binding protein DExH-Box helicase 9 (DHX9) in hepatocellular carcinoma (HCC) radioresistance and molecular mechanisms. HCC tissues were compared with adjacent normal liver tissues by bioinformatics analysis. Clinical samples were evaluated according to RECIST 1.1 criteria. Regulatory interactions between EEF1A2 and DHX9 were analyzed. The effect of targeting these genes on HCC radioresistance was assessed. EEF1A2 was significantly elevated in radiation-resistant HCC tissues and cell lines. EEF1A2 overexpression was associated with enhanced cellular proliferation, reduced apoptosis, increased metastatic potential. Decreasing EEF1A2 significantly improved radiosensitivity. DHX9 stabilized EEF1A2 mRNA and increased EEF1A2 expression. Inhibition of DHX9 produced similar radiosensitizing effects as those observed with EEF1A2 knockdown. The interaction between DHX9 and EEF1A2 activated the PI3K/Akt pathway. The DHX9/EEF1A2 axis plays a pivotal role in the radioresistance of HCC by modulating the PI3K/Akt pathway.

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rna结合蛋白DHX9通过增强EEF1A2 mRNA稳定性激活PI3K/Akt通路增强转移性肝细胞癌的放射耐药

本研究阐明了真核延伸因子1 α 2 （EEF1A2）和rna结合蛋白DExH-Box解旋酶9 （DHX9）在肝细胞癌（HCC）放射耐药中的作用及其分子机制。采用生物信息学方法将HCC组织与邻近正常肝组织进行比较。临床样本按照RECIST 1.1标准进行评价。分析EEF1A2与DHX9之间的调控相互作用。评估靶向这些基因对HCC放射耐药的影响。EEF1A2在耐辐射HCC组织和细胞系中显著升高。EEF1A2过表达与细胞增殖增强、细胞凋亡减少、转移潜能增加相关。降低EEF1A2显著改善放射敏感性。DHX9稳定EEF1A2 mRNA，增加EEF1A2表达。抑制DHX9产生与EEF1A2敲除相似的放射增敏效应。DHX9和EEF1A2的相互作用激活了PI3K/Akt通路。DHX9/EEF1A2轴通过调节PI3K/Akt通路在HCC的放射耐药中起关键作用。

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来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.