14,15-epoxyeicosatrienoic acid drives intestinal adenoma growth and its value as an early biomarker for intestinal adenoma occurrence.

IF 6.4 2区医学 Q1 ONCOLOGY

Oncogenesis Pub Date : 2026-03-11 DOI:10.1038/s41389-026-00604-6

Shihui He, Ruyu Zeng, Bobing Zheng, Lingbi Jiang, Jinghong Zhu, Jiangchao Li

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引用次数: 0

Abstract

Intestinal adenomas are premalignant lesions that develop into colorectal cancer (CRC), yet the metabolic pathways underlying their malignant transformation remain poorly characterized. Using targeted metabolomics via ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we found that serum levels of the bioactive lipid metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET) were dramatically elevated in Apc^Min/+ adenoma model mice as early as pre-adenoma stages, compared to C57BL/6 controls. The results were also consistent in adenomas and CRC patients. ELISA data and bioinformatics analyses revealed both elevated serum 14,15-EET levels and upregulated cytochrome P450 2J2 (CYP2J2) expression in tumor. Functional studies showed that 14,15-EET accelerates adenoma growth in vivo, and promotes proliferation, migration, and invasion in vitro by activating AKT (Ser473)/ERK1/2 signaling and inducing epithelial-mesenchymal transition (EMT). Its early elevation in premalignant lesions, and relative molecules 14,15-EET/CYP2J2 represents a novel strategy for disrupting adenoma-carcinoma transition, and offering new biomarker for CRC prevention.

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14,15-环氧二碳三烯酸驱动肠腺瘤生长及其作为肠腺瘤发生的早期生物标志物的价值。

肠腺瘤是发展为结直肠癌（CRC）的癌前病变，但其恶性转化的代谢途径仍不清楚。通过超高效液相色谱-串联质谱（UPLC-MS/MS）的靶向代谢组学方法，我们发现ApcMin/+腺瘤模型小鼠早在腺瘤前期，血清中生物活性脂质代谢物14,15-环氧二碳三烯酸（14,15- eet）水平就显著升高，与C57BL/6对照组相比。结果在腺瘤和结直肠癌患者中也是一致的。ELISA数据和生物信息学分析显示，肿瘤中血清14、15-EET水平升高，细胞色素P450 2J2 （CYP2J2）表达上调。功能研究表明，14,15- eet通过激活AKT (Ser473)/ERK1/2信号，诱导上皮-间质转化（EMT），在体内加速腺瘤生长，并在体外促进腺瘤的增殖、迁移和侵袭。它在癌前病变中的早期升高，以及相关分子14,15- eet /CYP2J2代表了一种破坏腺瘤-癌转化的新策略，并为预防结直肠癌提供了新的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncogenesis ONCOLOGY-

CiteScore

11.90

自引率

0.00%

发文量

审稿时长

26 weeks

期刊介绍： Oncogenesis is a peer-reviewed open access online journal that publishes full-length papers, reviews, and short communications exploring the molecular basis of cancer and related phenomena. It seeks to promote diverse and integrated areas of molecular biology, cell biology, oncology, and genetics.