Nuclear factor-κB p65 regulates glutaminase I expression in human hepatocellular carcinoma

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: CLS1 and GLS2. Elevated CiLSl contributes to tumorigenesis andt umor progression. This study investigates the molecular mechanism by which GLS1 is regulated in human hepatocellular carcinoma (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-kappa B (NF-kappa B) 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-kappa B 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. Conclusion: GLS1 can be developed as a diagnostic and therapeutic target for human HCC.