PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer.
PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer.
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PHKG2调控幽门螺杆菌相关胃癌中RSL3诱导的铁死亡。
DOI：
10.1016/j.abb.2023.109560
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发表时间：
2023-03
影响因子：
3.9
通讯作者：
Wenjie Zhu;Duanrui Liu;Yi Lu;Jingguo Sun;Jingyu Zhu;Yu Xing;Xiaoli Ma;Yunshan Wang;M. Ji-M.-J
中科院分区：
文献类型：
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作者：
Wenjie Zhu;Duanrui Liu;Yi Lu;Jingguo Sun;Jingyu Zhu;Yu Xing;Xiaoli Ma;Yunshan Wang;M. Ji-M.-J
铁下垂是一种新发现的由铁依赖性脂质过氧化引起的调节性细胞死亡形式。幽门螺杆菌（Helicobacter pylori， H. pylori）感染被认为是胃癌（gastric cancer， GC）发生的高危因素，与活性氧水平升高和致癌信号通路激活有关。然而，GC是否在感染h。幽门紧闭与铁下垂的关系尚不清楚。在本研究中，我们证明了。幽门菌感染增加了GC细胞对RSL3 （RAS-selective lethal3）诱导的铁下垂的敏感性。嗜铁相关基因介导的分子亚型与肿瘤微环境（tumor microenvironment， TME）细胞浸润和患者生存有关。重要的是，我们发现磷酸化酶激酶G2 （PHKG2）的表达与h显著相关。幽门感染，代谢生物学过程，患者生存和治疗反应。我们进一步发现了h的机理。幽门螺杆菌诱导的细胞对铁下垂的敏感性涉及PHKG2对脂氧合酶花生四烯酸5-脂氧合酶（ALOX5）的调节。综上所述，PHKG2促进了rsl3诱导的铁下垂。通过促进ALOX5的表达。这些发现可能有助于更好地理解h的独特发病机制。幽门诱导的GC，并允许遗传，细胞和免疫治疗在不同情况下控制铁下垂的最大功效。
Ferroptosis is a newly discovered form of regulatory cell death induced by iron-dependent lipid peroxidation. Infection with Helicobacter pylori (H. pylori) is regarded as a high-risk factor for the development of gastric cancer (GC) and is associated with an increase in the levels of reactive oxygen species with activation of oncogenic signaling pathways. However, whether GC arising in the context of infection withH. pyloriis correlated with ferroptosis is still unknown. In this study, we demonstrate thatH. pyloriinfection increased the sensitivity of GC cells to RSL3 (RAS-selective lethal3)-induced ferroptosis. The molecular subtypes mediated by ferroptosis-related genes are associated with tumor microenvironment (TME) cell infiltration and patient survival. Importantly, we identified that the expression of phosphorylase kinase G2 (PHKG2) was remarkably correlated withH. pyloriinfection, metabolic biological processes, patient survival and therapy response. We further found the mechanism ofH. pylori-induced cell sensitivity to ferroptosis, which involves PHKG2 regulation of the lipoxygenase enzyme Arachidonate 5-Lipoxygenase (ALOX5). In conclusion, PHKG2 facilitates RSL3-induced ferroptosis inH. pylori-positive GC cells by promoting ALOX5 expression. These findings may contribute to a better understanding of the unique pathogenesis ofH. pylori-induced GC and allow for maximum efficacy of genetic, cellular, and immune therapies for controlling ferroptosis in diverse contexts.