SLC7A11 promotes the progression of gastric cancer and regulates ferroptosis through PI3K/AKT pathway

Objective: Ferroptosis is a form of regulated cell death that occurs depending on iron and reactive oxygen species (ROS), but the underlying molecular mechanisms remain poorly understood. The aim of our study was to investigate the role of solute carrier family 7 member 11(SLC7A11) in the progression of gastric cancer (GC) and its molecular mechanism. Method: The expression of SLC7A11 in GC was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blot. SLC7A11 interference and overexpression vector was constructed in vitro, transfected into GC cells, and the high efficiency plasmid vector fragment was screened.CCK-8 assay was used to detect the effect of cell proliferation. The migration ability of cells was detected by transwell assay. The mitochondrial structure was observed by transmission electron microscopy. CCK-8 assay was also used to detect the effect of SLC7A11 on the growth inhibition rate of ferroptosis in GC cells. The level of malondialdehyde (MDA), the ultimate product of lipid peroxidation, was detected by micromethod. The effect of SLC7A11 on PI3K/AKT signaling pathway was detected by Western blot. Results: SLC7A11 was significantly overexpressed in GC tissues than that in adjacent tissues. Knockdown of SLC7A11 inhibits cell proliferation, cell migration and invasion of GC, and increases the sensitivity of ferroptosis via moderating ROS and lipid peroxidation. Besides, overexpression of the SLC7A11 in GC cells reverses erastininduced ferroptosis partially. Mechanistically, we reveal that suppression of SCL7A11 leads to inactivity of PI3K/ AKT signaling pathway and further enhancing ferroptosis related lipid peroxidation, and thereby inhibiting GC progression. Conclusion: SLC7A11 plays an oncogene role in malignant progression of GC. SLC7A11 reversely regulates ferroptosis of GC cells by activating PI3K/AKT signaling pathway. Silencing SLC7A11 expression can inhibit the progression of GC.