GOT2 Elevation Mediated by YY1 Promotes the Tumorigenesis and Immune Escape of Lung Adenocarcinoma

Glutamate-oxaloacetate transaminase 2 (GOT2) has been demonstrated to contribute to lung cancer cell growth, invasion, migration and angiogenesis. Herein, we further probed the functions of GOT2 on lung adenocarcinoma (LUAD) cell ferroptosis and immune escape and its associated mechanism. qRT-PCR and Western blot analysis analyses were used to detect the levels of GOT2, and Yin Yang 1 (YY1). A mouse xenograft model was established for in vivo analysis. CCK-8, 5-ethynyl-2'-deoxyuridine, and wound healing assays were applied for the detection of cell proliferation and migration. Cell ferroptosis was evaluated by flow cytometry and the levels of malondialdehyde (MDA) and Fe2+. Immune escape was assessed by measuring CD8+ T cell apoptosis and programmed death-1 ligand 1 (PD-L1) levels. The interaction between GOT2 and YY1 was determined using Chromatin immunoprecipitation and dual luciferase reporter assays. GOT2 expression was higher in LUAD tissues and cells, and the silencing of GOT2 impeded LUAD growth in vivo. Further loss-of-function assays showed that GOT2 silencing suppressed LUAD cell proliferation, migration and immune escape, and induced ferroptosis. Mechanically, we found that YY1 activated the transcription of GOT2 and could elevate GOT2 expression. Moreover, YY1 silencing repressed LUAD cell proliferation, migration and immune escape, and evoked ferroptosis, while theses effects could be reversed by GOT2 overexpression. YY1 activated GOT2 and elevated the expression of GOT2, which then promoted LUAD cell growth, migration and immune escape, and suppressed cell ferroptosis, suggesting a novel perceptivity for the treatment of LUAD.