NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells.

Recent studies revealed that NOP2/Sun RNA methyltransferase 5 (NSUN5) - ferritin heavy chain (FTH1) pathway is associated with ferroptosis in stem cells, whereas its roles in gastric cancer are still unclear. Our study aims to investigate the roles of the NSUN5-FTH1 axis in gastric cancer (GC) and its molecular mechanisms. Stable cell lines were constructed on SGC7901 cells by using shRNAs and pcDNA3.1 expression vectors, respectively. CCK-8 kits were used to determine cell viability. Biochemicals assays were used to detect lipid reactive oxygen species (ROS) and intracellular Fe levels. RNA immunoprecipitation assay, qPCR, and Western blotting were used to determine the changes in biomarkers. GC xenograft mouse model was established to confirm the observation in vivo. An elevation of NSUN5 was observed in GC tumor tissues. NSUN5 inhibited ferroptosis including decreasing cell viability and increasing levels of lipid ROS and Fe in GC cells. Besides, a positive correlation was also observed between NSUN5 and FTH1. Interestingly, NSUN5 regulated the levels of FTH1, instead of FTH1 regulating NSUN5 in GC cells. NSUN5-FTH1 axis regulated erastin-induced ferroptosis in SGC7901 cells. Consistently, silencing NSUN5 or FTH1 inhibited the growth of the SGC7901 tumor in vivo. NSUN5-FTH1 axis promoted the growth of GC cells in part by the regulation of ferroptosis.