PKM2 promotes glioma progression by mediating CTNNB1 expression

• Published in: Neurological research (New York) Vol. 46; no. 7; p. 583
• Main Authors: Ma, Chunyang, Feng, Yuan, Zhong, Kaiyi, Wei, Jiali
• Format: Journal Article
• Language: English
• Published: England 02.07.2024
• Subjects: Animals; Apoptosis - physiology; beta Catenin - genetics; beta Catenin - metabolism; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line, Tumor; Cell Movement - physiology; Cell Proliferation; Disease Progression; Gene Expression Regulation, Neoplastic; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Humans; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Nude; Pyruvate Kinase - genetics; Pyruvate Kinase - metabolism; Thyroid Hormone-Binding Proteins; Thyroid Hormones - genetics; Thyroid Hormones - metabolism; CTNNB1; epithelial-mesenchymal transition; Glioma; PKM2; glycolysis
• ISSN: 1743-1328
• DOI: 10.1080/01616412.2024.2337508

Glioma is a common intracranial tumor, exhibiting a high degree of aggressiveness and invasiveness. Pyruvate kinase M2 (PKM2) is overexpressed in glioma tissues. However, the biological role of PKM2 in glioma is unclear. The qRT-PCR, CCK-8, Transwell, flow cytometry detection, western blot assays, ELISA assay, and pyruvate kinase activity assays were performed in glioma cells transfected with PKM2 shRNA to explore the function of PKM2 in glioma progression. Then, STRING website was used to predict the proteins that interacted with PKM2, and Co-IP assay was conducted to further validate their interaction. Subsequently, the above experiments were performed again to find the effect of catenin beta 1 (CTNNB1) overexpression on PKM2-deficient glioma cells. The transplanted tumor models were also established to further validate our findings. PKM2 was up-regulated in glioma cells and tissues. After inhibiting PKM2, the proliferation, migration, glycolysis, and EMT of glioma cells were significantly decreased, and the proportion of apoptosis was increased. The prediction results of STRING website showed that CTNNB1 and PKM2 had the highest interaction score. The correlation between CTNNB1 and PKM2 was further confirmed by Co-IP test. PKM2 knockdown suppressed glioma cell proliferation, migration, glycolysis, and EMT, while CTNNB1 overexpression rescued these inhibitory effects. Correspondingly, PKM2 knockdown inhibited glioma growth in vivo. In summary, these findings indicated that PKM2 promotes glioma progression by mediating CTNNB1 expression, providing a possible molecular marker for the clinical management of gliomas.