AKR1B1 Inhibits Ferroptosis and Promotes Gastric Cancer Progression via Interacting With STAT3 to Activate SLC7A11

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Kaiyan Yang, Xin Zhang, Fei Long, Jing Dai
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引用次数: 0

Abstract

Gastric cancer (GC) is a frequently diagnosed malignant tumor in clinical settings; however, the mechanisms underlying its tumorigenesis remain inadequately understood. In this study, we identified significantly elevated expression levels of AKR1B1 in GC tissues through quantitative polymerase chain reaction (qPCR) and western blotting assays. Furthermore, a negative correlation was established between patient survival probability and AKR1B1 expression levels. Functionally, our experiments, including colony formation, transwell migration, and xenograft assays, demonstrated that the depletion of AKR1B1 inhibited the proliferation and progression of GC cells both in vivo and in vitro. Additionally, the assessment of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and mitochondrial morphology confirmed that AKR1B1 depletion induces ferroptosis. Mechanistically, we found that AKR1B1 interacts with STAT3, which subsequently activates SLC7A11. Notably, the ferroptosis induced by AKR1B1 depletion could be reversed by the overexpression of SLC7A11, thereby substantiating these interactions. In conclusion, our findings identify AKR1B1 as a novel oncogene in GC and elucidate the mechanism involving the AKR1B1-STAT3-SLC7A11 pathway and ferroptosis, providing new insights for potential therapeutic strategies in the treatment of GC.

AKR1B1通过与STAT3相互作用激活SLC7A11抑制铁下垂并促进胃癌进展
胃癌(GC)是临床常见的恶性肿瘤;然而,其发生机制尚不清楚。在本研究中,我们通过定量聚合酶链反应(qPCR)和western blotting检测发现,AKR1B1在GC组织中的表达水平显著升高。此外,患者生存率与AKR1B1表达水平呈负相关。在功能上,我们的实验,包括集落形成、跨井迁移和异种移植试验,表明AKR1B1的缺失在体内和体外都抑制了GC细胞的增殖和进展。此外,对活性氧(ROS)、丙二醛(MDA)、谷胱甘肽(GSH)和线粒体形态的评估证实,AKR1B1缺失诱导铁下垂。在机制上,我们发现AKR1B1与STAT3相互作用,STAT3随后激活SLC7A11。值得注意的是,由AKR1B1缺失引起的铁死亡可以通过SLC7A11的过表达而逆转,从而证实了这些相互作用。总之,我们的研究结果确定了AKR1B1在胃癌中是一个新的致癌基因,并阐明了AKR1B1- stat3 - slc7a11通路与铁ptosis的机制,为胃癌治疗的潜在治疗策略提供了新的见解。
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来源期刊
Cell Biology International
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.
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