Background
Glutaminase (GLS), the key enzyme that catalyzes glutamine catabolism, facilitates the production of energy, building blocks, and factors resisting stresses. Two isoforms of GLS have been identified: GLS1 and GLS2. Elevated GLS1 contributes to tumorigenesis and tumor progression. This study investigates the molecular mechanism by which GLS1 is regulated in human hepatocellular carcinoma (HCC).
Conclusion
GLS1 can be developed as a diagnostic and therapeutic target for human HCC.
Methods
Online databases were investigated to search for factors that co-overexpress with GLS1. siRNA knockdown or chemical compounds were utilized to manipulate the activation or inactivation of nuclear factor-κB (NF-κB) p65 signaling. Both the mRNA and protein levels of GLS1 were detected. The biological and clinical importance of p65-GLS1 in HCC was also demonstrated.
Results
NF-κB p65 regulates GLS1 expression in HCC cells. Knockdown or suppression of GLS1 compromises HCC cell proliferation. Elevated GLS1 expression correlates with neoplasm histological grade, and the dysregulation of p65-GLS1 is associated with poor prognosis in human HCC patients.