Helicobacter pylori Suppress the Ferroptosis of Gastric Cancer via Inhibiting NAE1-Mediated Neddylation of TFR1

<i>Helicobacter pylori (H. pylori)</i> infection promotes the progression of gastric cancer. The purpose of this study is to investigate the effects of <i>H. pylori</i> infection on gastric cancer and the underlying mechanisms. mRNA levels were determined by reverse transcription quantitative PCR (RT-qPCR). Protein expression was detected by Western blot. Cell viability was detected by Cell Counting Kit-8 assay. Cell proliferation was detected by colony formation assay. Cell mobility was detected by transwell assay. The co-localization of NEDD8 activating enzyme E1 subunit 1 (NAE1) and transferrin receptor 1 (TFR1) was determined by fluorescence <i>in situ</i> hybridization (FISH) assay. TFR1 neddylation was determined using <i>in vitro</i> neddylation assay. <i>H. pylori</i> infection contributed to the proliferation, migration, and invasion of gastric cancer. Moreover, <i>H. pylori </i>infection inhibited erastin-induced ferroptosis of gastric cancer cells. <i>H. pylori </i>infection downregulated NAE1, which promoted the neddylation and protein stability of TFR1. Intriguingly, overexpressed NAE1 inhibited the metastasis as well as promoted the ferroptosis of gastric cancer. <i>H. pylori </i>infection mediates malignant behaviors of gastric cancer via inactivating NAE1/TFR1 signaling. Therefore, targeting NAE1/TFR1 signaling may provide a novel strategy for gastric cancer.