LOXL3 Silencing Hampers the Metastasis and Angiogenesis of Gastric Cancer Cells Dependent on Ferroptosis Activation.

Gastric cancer (GC) remains a major unmet clinical problem accountable for considerable incidence and fatality rate. Lysyl oxidase-like 3 (LOXL3) has been recognized to be overexpressed in GC. Our work was meant to disclose the significance of LOXL3 in the advancement of GC and the likely action mechanism. LOXL3 expression in GC tissues and its correlation with the outcome of GC patients were investigated through bioinformatics tools. RT-qPCR and western blotting inspected LOXL3 expression in GC cells. CCK-8 method, EDU, as well as colony formation assays assayed cell proliferation. The capacities of cells to migrate and invade were appraised by wound healing and transwell assays, severally. Tube formation assay and ELISA measured angiogenesis. TBARS, C11 BODIPY staining, and FerroOrange estimated ferroptosis. Western blotting examined the expression of proteins implicated in metastasis and ferroptosis. The up-regulation of LOXL3 expression was noticed in GC tissues and cells, which was also associated with the poor outcome of GC patients. When LOXL3 was underexpressed, the proliferation, migration, invasion, epithelial-mesenchymal transition, and angiogenesis of GC cells were all halted. In addition, LOXL3 deletion resulted in the activation of ferroptosis in GC cells, and ferrostatin-1 (Fer-1), the specific ferroptosis inhibitor, compensated the suppressive role of LOXL3 down-regulation in the proliferation, metastasis, and angiogenesis of GC cells in vitro. All in all, knockdown of LOXL3 may serve an activator of ferroptosis to obstruct the aggressive process of GC.