Mitochondrial Ribosomal Protein S17 Silencing Inhibits Proliferation and Invasiveness of Lung Cancer Cells.

Abstract

Chromosomal alterations are frequent events in lung cancer progression. Although gains and losses of chromosomal position have been reported, the association between copy number alteration and lung cancer patient survival has not been extensively investigated. In this study, we performed a meta-analysis of public cBioPortal datasets spanning 25 lung cancer studies to identify putative cancer driver genes with copy number alterations associated with overall patient survival. Ten copy-number altered genes enriched in deceased lung cancer patients were identified. Seven of these putative driver genes were located in the 7p11.2 chromosomal location, and two were in the 9p21.3 cytoband. Among these genes, the mitochondrial ribosomal protein S17 (MRPS17) amplification was significantly associated with a lower patient survival rate (P = 1.47e-7). To investigate the functional role of MRPS17, small interfering RNA-mediated knockdown was performed in two non-small cell lung cancer cell lines, A549 and NCI-H460. MRPS17 knockdown significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth in both cell lines. Furthermore, knockdown of MRPS17 decreased the activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, suggesting its role in driving lung cancer progression through this critical oncogenic pathway. Our findings highlight MRPS17 as a potential cancer therapy target and a prognostic biomarker that may improve the survival rates of lung cancer patients. Future studies should explore its inhibition as a therapeutic strategy as well as elucidate its molecular mechanisms in cancer progression.