Abstract
Background: Metabolic reprogramming is a major feature of many tumors including NSCLC. Branched-chain alpha-keto acid dehydrogenase kinase (BCKDK) plays an important role in diabetes, obesity, and other diseases. However, the function of BCKDK in non-small cell lung cancer (NSCLC) is unclear. This study aimed to explore the function of BCKDK in NSCLC. Methods: Metabolites in the serum of patients with NSCLC and the supernatant of NSCLC cell cultures were detected using nuclear magnetic resonance (NMR) spectroscopy. Colony formation, cell proliferation, and cell apoptosis were assessed to investigate the function of BCKDK in the progression of NSCLC. Glucose uptake, lactate production, cellular oxygen consumption rate, extracellular acidification rate, and reactive oxygen species (ROS) were measured to examine the function of BCKDK in glucose metabolism. The expression of BCKDK was measured using reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemical assay. Results: Compared with healthy controls and postoperative NSCLC patients, increased BCAA and decreased citrate were identified in the serum of preoperative NSCLC patients. Upregulation of BCKDK affected the metabolism of branched-chain amino acids (BCAAs) and citrate in NSCLC cells. Knockout of BCKDK decreased the proliferation and exacerbated apoptosis of NSCLC cells ex vivo, while increased oxidative phosphorylation and, ROS levels, and inhibited glycolysis. Conclusions: BCKDK may influence glycolysis and oxidative phosphorylation by regulating the degradation of BCAA and citrate, thereby affecting the progression of NSCLC.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| ISSN: | 2218-6751 |
| Sprache: | Englisch |
| Dokumenten ID: | 102936 |
| Datum der Veröffentlichung auf Open Access LMU: | 05. Jun. 2023, 15:41 |
| Letzte Änderungen: | 17. Okt. 2023, 15:12 |
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