PLOD3 Variably Regulates Diverse Phenotypes in Human Cancer Cells

PLOD3 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3) is an essential enzyme that modifies collagen and contributes to collagen assembly and function. PLOD3 expression has been linked to human cancers and patient prognosis, although how PLOD3 regulates tumorigenesis is poorly understood. In this study we first examined the association between PLOD3 expression and human cancer survival and found that, in contrast to previous reports, PLOD3 expression was not significantly correlated with overall survival in cancers. We then studied how decreasing and increasing PLOD3 levels affected the phenotypes of HeLa, HT-1080, and HCT116 cells, three diverse and representative human cancer cell lines. Altering PLOD3 expression elicited a variable effect on the cell cycle and cell migration in the three cell lines. However, increased PLOD3 induced apoptosis, elevated the mitochondrial membrane potential, and reduced the reactive oxygen species (ROS) levels in all three cell lines, whereas decreasing PLOD3 had the opposite effects. Subsequent global mRNA expression analyses revealed changes in biological processes and pathways that were consistent with these phenotypic changes and suggested that apoptosis and mitochondrial metabolism might be two important mechanisms by which PLOD3 regulates cell behaviors.