2. Academic Validation
  3. PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer

PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer

  • Arch Biochem Biophys. 2023 Mar 20;109560. doi: 10.1016/j.abb.2023.109560.
Wenshuai Zhu 1,  Duanrui Liu 2,  Yi Lu 3,  Jingguo Sun 4,  Jingyu Zhu 5,  Yuanxin Xing 1,  Xiaoli Ma 1,  Yunshan Wang 1,  Mingyu Ji 6,  Yanfei Jia 7
Affiliations

Affiliations

  • 1 Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China; Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, 250013, People's Republic of China.
  • 2 Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China; Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China.
  • 3 Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, 250013, People's Republic of China.
  • 4 Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China.
  • 5 Department of Gastroenterology, Jinan Central Hospital, Shandong First Medical University, Jinan, 250013, People's Republic of China.
  • 6 Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China. Electronic address: labmedzxyy@163.com.
  • 7 Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China; Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, 250013, People's Republic of China. Electronic address: jiayanfei_@126.com.
PMID: 36948350 DOI: 10.1016/j.abb.2023.109560
Abstract

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 with H. pylori is correlated with Ferroptosis is still unknown. In this study, we demonstrate that H. pylori Infection 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 with H. pylori Infection, metabolic biological processes, patient survival and therapy response. We further found the mechanism of H. 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 in H. pylori-positive GC cells by promoting ALOX5 expression. These findings may contribute to a better understanding of the unique pathogenesis of H. pylori-induced GC and allow for maximum efficacy of genetic, cellular, and immune therapies for controlling Ferroptosis in diverse contexts.

Keywords

Ferroptosis; Gastric cancer; H. pylori; PHKG2; RSL3.

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