EPHX4, a member of the epoxide hydrolase family, is involved in various biological processes. Although its exact function remains not fully elucidated, studies suggest it may play a role in lipid metabolism as it was found localized on the surface of lipid droplets in sebocytes, and its depletion increased lipid droplet size and sebaceous lipogenesis [3].

In cancer research, EPHX4 has emerged as a significant factor. It is highly expressed in laryngeal, colorectal, pancreatic, and rectal cancers, and is associated with poor prognosis in laryngeal and pancreatic cancers [1,2,4,5]. In laryngeal cancer, it promotes cell line proliferation, colony formation, and invasion, and participates in NK cell-mediated cytotoxicity [1]. In colorectal cancer, it promotes the malignant phenotype of CRC cells [2]. In pancreatic cancer, knockdown of EPHX4 significantly decreased cell migration, proliferation, and invasion [4].

In summary, EPHX4 appears to be involved in lipid metabolism in sebocytes and has tumor-promoting effects in multiple cancer types. These findings from various cancer-related studies highlight the potential of EPHX4 as a prognostic biomarker and a druggable target in cancer treatment [1,2,4,6].

References:

1. Shen, Nimei, Gao, Gang, Lu, Xinhong, Qian, Maohua, Qin, Yang. 2024. Comprehensive analysis of the immune implication of EPHX4 gene in laryngeal squamous cell carcinoma. In Brazilian journal of otorhinolaryngology, 90, 101411. doi:10.1016/j.bjorl.2024.101411. https://pubmed.ncbi.nlm.nih.gov/38663041/

2. Cao, Lichao, Ba, Ying, Chen, Fang, Zhang, Shenrui, Zhang, Hezi. 2025. The prognostic significance of epoxide hydrolases in colorectal cancer. In Biochemistry and biophysics reports, 41, 101912. doi:10.1016/j.bbrep.2024.101912. https://pubmed.ncbi.nlm.nih.gov/39850362/

3. Dahlhoff, Maik, Fröhlich, Thomas, Arnold, Georg J, Zouboulis, Christos C, Schneider, Marlon R. 2014. Characterization of the sebocyte lipid droplet proteome reveals novel potential regulators of sebaceous lipogenesis. In Experimental cell research, 332, 146-55. doi:10.1016/j.yexcr.2014.12.004. https://pubmed.ncbi.nlm.nih.gov/25523620/

4. Huang, Shaoyang, Gu, Dandan, Xiong, Wei. 2025. Exploring the functional and prognostic roles of EPHX4 in pancreatic cancer: Insights from bioinformatics and experimental validation. In Gene, 959, 149504. doi:10.1016/j.gene.2025.149504. https://pubmed.ncbi.nlm.nih.gov/40258406/

5. Flebbe, Hannah, Hamdan, Feda H, Kari, Vijayalakshmi, Johnsen, Steven A, Grade, Marian. 2019. Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer. In Cancers, 11, . doi:10.3390/cancers11081142. https://pubmed.ncbi.nlm.nih.gov/31404997/

6. Özenver, Nadire, Efferth, Thomas. 2023. Identification of Prognostic and Predictive Biomarkers and Druggable Targets among 205 Antioxidant Genes in 21 Different Tumor Types via Data-Mining. In Pharmaceutics, 15, . doi:10.3390/pharmaceutics15020427. https://pubmed.ncbi.nlm.nih.gov/36839749/