mRNA-seq analysis of S100A16-mediated alternative splicing in lung adenocarcinoma under oxidative stress

Lung adenocarcinoma (LUAD) cells develop adaptive mechanisms to survive high oxidative stress in the tumor microenvironment. This study aims to elucidate the role of S100A16, a calcium-binding protein, in regulating mitochondrial quality control and oxidative stress resistance. We performed polyA-enriched mRNA sequencing on human lung adenocarcinoma A549 cells with stable knockdown of S100A16, hnRNPM (a splicing factor identified as S100A16 interactor) or MagoHB (a negative control interactor), with or without 100μM H₂O₂ treatment for 2 hours (3 biological replicates per group). Transcriptomic analysis revealed that S100A16 translocates to the nucleus under oxidative stress and interacts with hnRNPM to modulate alternative splicing of mitochondrial genes (e.g., LETMD1), thereby maintaining mitochondrial morphology, membrane potential and respiratory function. These data provide mechanistic insights into S100A16 as a potential therapeutic target for LUAD.