NR3C2 inhibits glycolysis in non-small cell lung cancer cells by regulating the Akt pathway

Background: Uncertainty surrounds the function of Nuclear Receptor Subfamily 3 Group C Member 2 (NR3C2) in controlling glycolysis in non-small cell lung cancer (NSCLC) and its molecular relationship to the Akt (Protein kinase B) pathway. In a number of malignancies, NR3C2 has been identified as a tumor suppressor. This research attempts to show how NR3C2 inhibits the development of NSCLC. Methods: The expression of NR3C2 and its impact on patient survival in NSCLC were investigated using a public database. Following NR3C2 overexpression via plasmid transfection, cell viability was assessed using Cell Counting Kit-8 (CCK8) assays. The colony formation assay was used to evaluate cell proliferation. Adenosine Triphosphate (ATP) generation, glucose uptake, and lactate production were measured in cells using appropriate kits. Cell apoptosis was assessed by flow cytometry. Western blotting was employed to evaluate protein expression levels of NR3C2, cleaved- Poly ADP-ribosepolymerase (PARP), cleaved-caspase3, Glucose transporter 1 (GLUT1), hexokinase2 (HK2), p-Akt/Akt and p-mammalian target of rapamycin (mTOR)/mTOR. Results: Database analysis revealed reduced NR3C2 expression in tumor. Overexpression of NR3C2 resulted in increased apoptosis and impaired colony formation and cell survival, and inhibited glucose consumption, lactate production and ATP levels. Furthermore, apoptotic indicators cleaved-PARP and cleaved-caspase3 showed markedly increased protein levels, whereas p-Akt/Akt, p-mTOR/mTOR, GLUT1 and HK2 showed markedly decreased levels. Conclusions: NR3C2 suppresses NSCLC cell proliferation and glycolysis, potentially through the suppression of the Akt pathway.

NSCLC; NR3C2; Proliferation; Glycolysis; Apoptosis; Akt

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