Exploring mitochondrial ribosomal protein S12 as a novel target for non-small cell lung cancer.

This study investigates the expression and functional significance of mitochondrial ribosomal protein S12 (MRPS12) within NSCLC pathogenesis. The Cancer Genome Atlas dataset reveals a significant association between MRPS12 overexpression and unfavorable clinical outcomes in NSCLC patients. Single-cell RNA sequencing data unequivocally confirm MRPS12 overexpression across diverse NSCLC cancer cell populations. MRPS12 is also upregulated in locally-treated NSCLC tissues. shRNA-mediated gene silencing or CRISPR-Cas9-mediated gene knockout (KO) of MRPS12 impaired mitochondrial function, resulting in a reduction in oxygen consumption rate, marked declines of complex I activity and ATP levels, mitochondrial membrane depolarization, and an increase in reactive oxygen species production in NSCLC cells. Moreover, MRPS12 silencing or knockout attenuated cell viability, proliferation, and migratory capacity, while inducing apoptotic cell death in various NSCLC cell types. Conversely, ectopic MRPS12 overexpression conferred a pro-tumorigenic phenotype to NSCLC cells. In vivo studies demonstrated that MRPS12 silencing markedly inhibited the growth of subcutaneous xenografts derived from primary NSCLC cells in nude mice. The MRPS12-silenced NSCLC xenografts exhibited decreased ATP levels, elevated oxidative injury, diminished proliferation, inhibited Akt-mTOR activation and an increase in apoptosis. These findings support the important role of MRPS12 in supporting mitochondrial function and driving the malignant progression of NSCLC.