{"title":"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","authors":"Qichao Hong, Shuzhou Liu, Qimeng Zhang, Shun Ding, Chengliang Xing, Jingren Yan, Liuyang Zhang, Zhonglin Mu","doi":"10.1002/jbt.70450","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>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 (<i>p</i> < 0.01). Overexpression of miR-4713-3p markedly enhanced cell proliferation (<i>p</i> < 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 (<i>p</i> < 0.01), whereas EPHX3 overexpression suppressed these changes and inhibited EMT. In vivo, miR-4713-3p knockdown suppressed tumor growth in xenograft models (<i>p</i> < 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.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of MicroRNA-4713-3p on Promoting Malignant Progression of Nasopharyngeal Carcinoma via Targeted Inhibition of EPHX3 to Activate Wnt/β-Catenin Signaling Pathway\",\"authors\":\"Qichao Hong, Shuzhou Liu, Qimeng Zhang, Shun Ding, Chengliang Xing, Jingren Yan, Liuyang Zhang, Zhonglin Mu\",\"doi\":\"10.1002/jbt.70450\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>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 (<i>p</i> < 0.01). Overexpression of miR-4713-3p markedly enhanced cell proliferation (<i>p</i> < 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 (<i>p</i> < 0.01), whereas EPHX3 overexpression suppressed these changes and inhibited EMT. In vivo, miR-4713-3p knockdown suppressed tumor growth in xenograft models (<i>p</i> < 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.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 9\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70450\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70450","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.