TNKS1 Affects the Metabolism and Proliferation of Glioma via the PGC-1α Pathway

Abstract

Objective: Glioma is a primary central malignant tumor, but its curative effects and postoperative prognosis are still not ideal. Tankyrase1 (TNKS1) has been reported to promote the progression of glioma. This study aimed to assess the potential molecular mechanisms by which TNKS1 regulates the metabolism and proliferation of glioma. Methods: U87 and U251 cells with TNKS1 knockdown were established upon transfection using shRNA-TNKS1. Cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay, the glucose and lactic acid levels were measured using a biochemical detection kit. While reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were detected through flow cytometry. The Western blot assay was applied to check the expression levels of Akt, phosphorylated Akt (p-Akt), and glucose transporter type 1 (GLUT1). Besides, TNKS1-knockdown U87 and U251 cells were implanted to establish a nude mice xenograft model, followed by tumor growth monitoring. The apoptosis was evaluated using the Terminal-deoxynucleoitidyl transferase Mediated Nick End Labeling (TUNEL) assay and the immunohistochemical assay was applied to check the expression levels of peroxisome-proliferator-activated receptor γ coactivator (PGC)-1α, Akt, p-Akt, and GLUT1. Results: After knocking down TNKS1 in both U251 and U87 cells, the cell viability was significantly suppressed. The content of glucose, lactic acid, and PGC-1α was significantly downregulated, and the production of ROS was enhanced while the MMP level was reduced. Moreover, the Akt, p-Akt, and GLUT1 expressions were notably inhibited. The tumor growth was inhibited, and apoptosis was greatly induced in U87 and U251 xenograft tumor tissues, accompanied by the downregulation of PGC-1α, Akt, p-Akt, and GLUT1 in tumor tissues. Conclusions: Knockdown of TNKS1 could inhibit the metabolism and proliferation of glioma by mediating the PGC-1α.