GOLM1 silencing compromises mitochondrial function, proliferation, and invasion in lung cancer cells

GOLM1, a Golgi-resident protein, has been implicated in lung cancer progression and other pulmonary diseases. This study aimed to delineate the effects of GOLM1 silencing on lung adenocarcinoma cells and to elucidate the underlying molecular mechanisms. Silencing of GOLM1 in NCI-H1944 and A549 lung cancer cell lines resulted in reduced cellular proliferation, as measured by [ 3 H]thymidine incorporation, cell viability and invasion. Transcriptome analysis of A549 cells subjected to GOLM1 silencing revealed altered expression of genes associated with DNA replication and synthesis, cell cycle regulation, p53 signaling, and lysosomal function. Cell cycle profiling showed an accumulation of cells in the G1 phase, accompanied by increased apoptosis. Importantly, a marked reduction in maximal mitochondrial respiration rate was observed upon GOLM1 silencing. Consistently, genes involved in mitochondrial biogenesis and protein import were downregulated. Expression of an siRNA-resistant cDNA construct resulted in significant rescue of cell proliferation, invasion and mitochondrial respiration, validating the specificity of key functional effects of GOLM1 knockdown. Taken together, these findings suggest that GOLM1 contributes to the progression of lung cancer by modulating pathways associated with cellular energy metabolism, proliferation, invasion and survival, reinforcing its potential as a therapeutic target in lung adenocarcinoma.