TNKS1 mediates the PTEN-PI3K/AKT pathway to regulate glycolysis and proliferation in gliomas

Objective: To explore the mechanisms by which TNKS1 regulates glycolysis and proliferation in glioma.

Methods: Cell viability was assessed using the CCK-8 assay. Levels of glucose and lactate were measured using biochemical detection kits. Western blotting was used to detect the expression levels of glycolysis-related proteins, and qPCR was employed to measure the mRNA expression of GLUT1 and HK2. A subcutaneous xenograft tumor model in nude mice was established. After intratumoral injection of drugs, the effects of TNKS1 knockdown on tumor tissues were observed using HE staining and immunohistochemical staining. Western blotting was also used to detect the expression of PTEN and Other proteins in glioma tissues.

Results: Compared with the control group, TNKS1 knockdown resulted in increased expression of PTEN, decreased expression of PI3K and p-AKT/Akt proteins, reduced cell proliferation capacity, and lower glucose uptake and lactate production. The results were opposite in the TNKS1 overexpression group. In the group treated with a PI3K agonist compared with the untreated group, the expression of PI3K and p-AKT/Akt proteins increased, and cell proliferation capacity, glucose uptake, and lactate production also increased to varying degrees. In the TNKS1 overexpression + PI3K Inhibitor group compared with the TNKS1 overexpression group, the expression of PI3K and p-AKT/Akt proteins decreased, and cell proliferation capacity, glucose uptake, and lactate production also decreased to varying degrees. In the in vivo experiments, compared with the control group, the TNKS1 knockdown group showed increased tumor Cell Apoptosis and Necrosis. Immunohistochemical and Western blotting analyses indicated that compared with the TNKS1-siRNA empty vector group, the TNKS1-siRNA group had significantly increased PTEN protein expression. The expression levels of PI3K, p-AKT/Akt proteins, and Ki67 were significantly lower in the TNKS1-siRNA group, inhibitor group, and TNKS1-siRNA + inhibitor group.

Conclusion: TNKS1 regulates glycolysis and proliferation in glioma by mediating the PTEN-PI3K/Akt pathway.

Glioma; Glycolysis; PTEN-PI3K/AKT pathway; TNKS1.