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非小细胞肺癌中 ZEB1 泛素诱导的 FBXO45 表达水平与癌症严重程度的相关性。

Correlation of FBXO45 Expression Levels with Cancer Severity by ZEB1 Ubiquitin in Non-Small-Cell Lung Cancer.

机构信息

Department of Pathology, Xianyang Central Hospital, Xianyang City, 712000 Shaanxi Province, China.

Department of Pathology, Qianxian People's Hospital, Qianxian 713300, China.

出版信息

J Environ Pathol Toxicol Oncol. 2024;43(4):13-23. doi: 10.1615/JEnvironPatholToxicolOncol.2024053018.

Abstract

The early diagnostic methods for non-small-cell lung cancer (NSCLC) are limited, lacking effective biomarkers, and the late stage surgery is difficult and has a high recurrence rate. We investigated whether the effects of FBXO45 in arcinogenesis and metastasis of NSCLC. The up-regulation of FBXO45 expression in NSCLC patients or cell lines were observed. FBXO45 gene promoted metastasis and Warburg effect, and reduced ferroptosis of NSCLC. FBXO45 induced ZEB1 expression to promote Warburg effect and reduced ferroptosis of NSCLC. Sh-FBXO45 reduced cancer growth of NSCLC in mice model. FBXO45 decreased the ubiquitination of ZEB1, leading to increased expression of ZEB1, which in turn promoted the Warburg effect and reduced ferroptosis in NSCLC. In vivo imaging, Sh-FBXO45 also reduced ZEB1 expression levels of lung tissue in mice model. FBXO45 in NSCLC through activating the Warburg effect, and the inhibition of ferroptosis of NSCLC by the suppression of ZEB1 ubiquitin, FBXO45 may be a potential therapeutic strategy for NSCLC.

摘要

非小细胞肺癌(NSCLC)的早期诊断方法有限,缺乏有效的生物标志物,晚期手术难度大,复发率高。我们研究了 FBXO45 在 NSCLC 发生和转移中的作用。观察到 FBXO45 表达在 NSCLC 患者或细胞系中的上调。FBXO45 基因促进 NSCLC 的转移和 Warburg 效应,并降低铁死亡。FBXO45 诱导 ZEB1 表达促进 Warburg 效应并降低 NSCLC 的铁死亡。Sh-FBXO45 减少了 NSCLC 小鼠模型中的肿瘤生长。FBXO45 减少了 ZEB1 的泛素化,导致 ZEB1 表达增加,从而促进了 NSCLC 的 Warburg 效应和铁死亡减少。体内成像显示,Sh-FBXO45 还降低了 NSCLC 小鼠模型肺组织中的 ZEB1 表达水平。FBXO45 通过激活 Warburg 效应,并通过抑制 ZEB1 泛素抑制 NSCLC 的铁死亡,FBXO45 可能是 NSCLC 的一种潜在治疗策略。

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