MicroRNA-4713-3p通过靶向抑制EPHX3激活Wnt/β-Catenin信号通路促进鼻咽癌恶性进展的作用

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Qichao Hong, Shuzhou Liu, Qimeng Zhang, Shun Ding, Chengliang Xing, Jingren Yan, Liuyang Zhang, Zhonglin Mu
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引用次数: 0

摘要

鼻咽癌是头颈部常见的恶性肿瘤,其发展及预后受多种因素影响。环氧化物水解酶3 (EPHX3)是一种在炎症和肿瘤调节中发挥重要作用的酶。我们旨在探讨EPHX3在鼻咽癌中的表达模式和生物学功能。采用qRT-PCR技术检测EPHX3在鼻咽癌组织和细胞系中的表达谱。随后评估EPHX3表达与鼻咽癌患者临床特征的相关性。随后,我们在体外和体内验证了miR-4713在鼻咽癌中靶向EPHX3的机制。通过基因集富集分析和细胞实验证实ephx3调控的下游Wnt/β-catenin通路对鼻咽癌的进展和上皮间质转化(epithelial-mesenchymal transition, EMT)的影响。与邻近正常组织相比,EPHX3 mRNA在鼻咽癌组织中的表达显著下调(p < 0.01)。过表达miR-4713-3p可显著增强细胞增殖(p < 0.05)、迁移和侵袭,双荧光素酶和分子对接证实EPHX3是miR-4713-3p的直接靶点。在机制上,miR-4713-3p过表达后,Wnt/β-catenin通路的关键组分,包括β-catenin和c-Myc显著上调(p < 0.01),而EPHX3过表达抑制了这些变化并抑制了EMT。在体内,miR-4713-3p敲低抑制异种移植模型中的肿瘤生长(p < 0.05)。我们的研究揭示了EPHX3在鼻咽癌发展中的重要意义,并为EPHX3作为可能的治疗靶点提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Effect of MicroRNA-4713-3p on Promoting Malignant Progression of Nasopharyngeal Carcinoma via Targeted Inhibition of EPHX3 to Activate Wnt/β-Catenin Signaling Pathway

Effect of MicroRNA-4713-3p on Promoting Malignant Progression of Nasopharyngeal Carcinoma via Targeted Inhibition of EPHX3 to Activate Wnt/β-Catenin Signaling Pathway

Nasopharyngeal carcinoma (NPC) represents a common malignancy in the head-and-neck region, and its development and prognosis can be influenced by multiple factors. Epoxide hydrolase 3 (EPHX3) is an enzyme that perform crucial roles in inflammation and tumors regulation. We aim to discuss the expression pattern and biological function of EPHX3 in NPC. The EPHX3 expression patterns in NPC tissues and cell lines were determined by the qRT-PCR technique. Correlations between EPHX3 expression and the clinical characteristics of NPC patients were subsequently assessed. Afterwards, the mechanism of miR-4713 targeting EPHX3 in NPC was validated either in vitro or in vivo. Gene set enrichment analysis and cell experiments were conducted to prove the impact of the EPHX3-regulated downstream Wnt/β-catenin pathway on the progression of NPC and epithelial-mesenchymal transition (EMT). EPHX3 mRNA expression was significantly downregulated in NPC tissues compared with adjacent normal tissues (p < 0.01). Overexpression of miR-4713-3p markedly enhanced cell proliferation (p < 0.05), migration, and invasion, while dual-luciferase and molecular docking confirmed that EPHX3 is a direct target of miR-4713-3p. Mechanistically, key components of the Wnt/β-catenin pathway, including β-catenin and c-Myc, were significantly upregulated following miR-4713-3p overexpression (p < 0.01), whereas EPHX3 overexpression suppressed these changes and inhibited EMT. In vivo, miR-4713-3p knockdown suppressed tumor growth in xenograft models (p < 0.05). Our study reveals the significance of EPHX3 in the development of NPC and offers a basis for the promise of EPHX3 as a possible therapeutic target.

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来源期刊
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.
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