TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism.

ABSTRACT: Pancreatic cancer (PC) progresses rapidly, and gemcitabine-based chemotherapy has brought only limited efficacy. Identifying key drivers and therapeutic targets holds significant clinical value. In this study, through comprehensive analysis of multiple PC databases, this work identifies TRIM21 as a promising driver mediator. This work further performs loss- and gain-of-function assays for TRIM21, revealing that TRIM21 knockout inhibits tumor proliferation and gemcitabine resistance both in vitro and vivo. Lipidomics reveal that silencing TRIM21 reduce the arachidonic acid production, and inhibit ferroptosis. Mechanically, through proteomics, ubiquitomics, and liquid chromatography-tandem mass spectrometry analysis, the key metabolic enzyme of arachidonic acid -EPHX1 is identified as a down

SUBMITTER: Fan X 

PROVIDER: S-EPMC11848624 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature