This study investigated the role of the mitochondrial protein MRPL17 (mitochondrial ribosomal protein L17) in non-small cell lung cancer (NSCLC), exploring its expression profile, clinical significance, and therapeutic potential. Transcriptomic analyses of TCGA and single-cell RNA sequencing data revealed significant upregulation of MRPL17 in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma) tumor tissues, particularly within malignant epithelial and proliferating cancer cells. Elevated MRPL17 expression correlated with advanced stages, positive lymph node metastasis, and poorer overall survival. In vitro investigations demonstrated that silencing or knockout of MRPL17 attenuated cell viability, proliferation, migration, and invasion in NSCLC cells, while promoting apoptosis. Mechanistically, MRPL17 silencing impaired mitochondrial respiratory function, causing reduced oxygen consumption, diminished Complex I activity, and decreased ATP. These impairments were partially reversible by antioxidant treatment or glucose supplementation. Conversely, MRPL17 overexpression enhanced aggressive cellular phenotypes and mitochondrial energetic output. Bioinformatic analysis and subsequent experiments confirmed COX8A as a direct downstream target of MRPL17, mediating its pro-cancerous effects. In vivo, MRPL17 silencing suppressed NSCLC xenograft growth in nude mice, a phenomenon associated with reduced COX8A levels, mitochondrial dysfunction, heightened oxidative stress, and increased apoptosis. Thus, MRPL17 is an important pro-cancerous target in NSCLC, driving malignant progression through the regulation of mitochondrial function and cellular redox balance, with COX8A identified as a key mediator.
Mu et al. (Sun,) studied this question.