AUTHOR=Wen Jie , Aili Abudureyimujiang , Yan Yao Xue , Lai YuLin , Niu Shaoqing , He Shasha , Zhang Xiaokai , Zhang Guixiong , Li Jiaping 

TITLE=OIT3 serves as a novel biomarker of hepatocellular carcinoma by mediating ferroptosis via regulating the arachidonic acid metabolism

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.977348

DOI=10.3389/fonc.2022.977348

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Oncoprotein-Induced Transcript 3 Protein (OIT3) was identified as a liver-specific gene with abnormal expression in hepatocellular carcinoma (HCC). Herein, we aimed to examine the function and specific mechanism of OIT3 in HCC.</p></sec><sec><title>Methods</title><p>Bioinformatic analyses and tissue microarray <italic>via</italic> immunohistochemistry were used to validate the expression of OIT3 in HCC. The biofunctions of OIT3 in HCC were determined <italic>in vitro</italic> and <italic>in vivo</italic>. The mechanism was confirmed by RNA-Sequence and Western blotting. The uni- and multivariate analyses were used to identify the independent predictors for HCC.</p></sec><sec><title>Results</title><p>Low expression of OIT3 was observed in HCC and predicted a poor clinical outcome. Ectopic expression of OIT3 could inhibit the proliferation, migration, and invasion abilities of HCC cells. Mechanistically, OIT3 upregulated the expression of ALOX15 and CYP4F3, thus inducing arachidonic acid increase, ROS accumulation, and lipid peroxidation, and eventually causing ferroptosis. OIT3 was validated as a prognostic predictor for HCC patients.</p></sec><sec><title>Conclusions</title><p>Our findings revealed a novel role of OIT3 in the process of tumorigenesis of HCC. OIT3 inhibited reproliferation, migration, and invasion of HCC cells by triggering ferroptosis, which indicates that OIT3 could serve as a potential biomarker in HCC.</p></sec>