GOLPH3 inhibits erastin-induced ferroptosis in colorectal cancer cells

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Biology International Pub Date : 2024-06-02 DOI:10.1002/cbin.12190

Lihua Chen, Chunxiao Wang, Xiaojing Chen, Yuze Wu, Mingliang Chen, Xian Deng, Chengzhi Qiu

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引用次数: 0

Abstract

Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis-related genes in CRC. The overexpression of GOLPH3 in Erastin-induced Caco-2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT-29 CRC cells. GOLPH3 induced the expression of prohibitin-1 (PHB1) and prohibitin-2 (PHB2), which also inhibited ferroptosis in Erastin-treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2) in Caco-2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2.

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GOLPH3 可抑制大肠癌细胞中由麦拉宁诱导的铁蛋白沉积。

铁凋亡是一种新型的程序性细胞死亡形式，被认为是结直肠癌（CRC）治疗的药物靶点。然而，铁突变在 CRC 中的作用及其内在机制尚未完全明了。在本研究中，我们发现一种富含于高尔基体的蛋白质--高尔基磷蛋白 3（GOLPH3）在人类 CRC 组织和几种 CRC 细胞系中过表达。GOLPH3 的表达与 CRC 中铁蛋白沉积相关基因的表达密切相关。在Erastin诱导的Caco-2 CRC细胞中过表达GOLPH3可减少铁突变表型，而在HT-29 CRC细胞中敲除GOLPH3可增强铁突变。GOLPH3 可诱导 prohibitin-1 （PHB1）和 prohibitin-2 （PHB2）的表达，这也抑制了 Erastin 处理的 CRC 细胞的铁梭形细胞增多。此外，在 Caco-2 细胞中，GOLPH3 与 PHB2 和核因子红细胞 2 相关因子 2（NRF2）相互作用。这些观察结果表明，GOLPH3 是 CRC 细胞中铁细胞凋亡的负调控因子。GOLPH3通过诱导PHB1和PHB2的表达以及与PHB2和NRF2相互作用，保护这些细胞免于铁变态反应。

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

Cell Biology International 生物-细胞生物学

CiteScore

7.60

自引率

0.00%

发文量

208

审稿时长

1 months

期刊介绍： Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.