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

Helicobacter pylori (H. pylori) infection promotes the progression of gastric cancer. The purpose of this study is to investigate the effects of H. pylori 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 in situ hybridization (FISH) assay. TFR1 neddylation was determined using in vitro neddylation assay. H. pylori infection contributed to the proliferation, migration, and invasion of gastric cancer. Moreover, H. pylori infection inhibited erastin-induced ferroptosis of gastric cancer cells. H. pylori 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. H. pylori 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.