H3K27 acetylation activated-CCS regulates autophagy and apoptosis of lung cancer by alleviating oxidative stress

Abstract

Copper chaperone for superoxide dismutase (CCS) is abnormally expressed in various human malignancies. However, the function and mechanism of CCS in lung cancer progression remain unclear. In the current study, CCS protein and mRNA levels were found to be increased in lung adenocarcinoma (LUAD) tissue and cell lines. Patients with higher CCS levels had a poorer prognosis. Decreasing the enrichment of histone H3 Lys27 acetylation (H3K27ac) by A-485 inhibited CCS expression. CCS depletion upregulated reactive oxygen species (ROS) levels, aggravated oxidative stress, inhibited autophagy, inhibited cell survival, and promoted apoptosis. The treatment of antioxidant N-Acetyl-L-cysteine (NAC) rescued these changes induced by CCS depletion. CCS also was found to be related to the immune infiltration of CD8 + T cells and regulatory T cells in LUAD. These data indicated that overexpression of CCS activated by H3K27 acetylation relieved oxidative stress, promoted autophagy, and inhibited apoptosis. CCS may be regarded as a potential therapeutic target for LUAD.