Inhibited proliferation and immune evasion of lung cancer: The key role of miR-4483 in lncRNA linc00824/miR-4483/PD-L1 pathway.

Growing evidence indicates that lactate and long non-coding RNAs (lincRNAs) exert a crucial influence on tumor development. This study aimed to investigate lactate-induced histone lactylation promotes the roles of lincRNA in lung cancer progression by enhancing proliferation and PD-L1-mediated inhibition of T cell antitumor function. Results showed that both linc00824 and lactate levels were elevated in NSCLC tissues compared to adjacent controls. Lactate upregulated linc00824 expression by regulating histone H3K18 lactylation. Functioning as an oncogene, linc00824 promoted NSCLC cell proliferation and migration. Furthermore, linc00824 upregulated PD-L1 expression through targeting miR-4483 in H1975 cells, thereby suppressing CD8+ T cell activation. MiR-4483 inhibited lung cancer cell proliferation and exhibited synergistic antitumor effects with envafolimab. In summary, lactate-induced histone lactylation drives linc00824 upregulation, facilitating lung cancer progression by enhancing tumor cell proliferation and suppressing T cell antitumor function via regulating miR-4483/PD-L1. We identified an antitumor strategy for lung cancer by using miR-4483.