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

Abstract

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.

Keywords: Wnt/β‐catenin pathway; epithelial‐mesenchymal transition (EMT); epoxide hydrolase 3; miR‐4713; miR‐4713‐3p; nasopharyngeal carcinoma.