Department of Neurosurgery, First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China.
Department of Immunology, Affiliated Children's Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shanxi, China.
Neurol Res. 2024 Jul;46(7):583-592. doi: 10.1080/01616412.2024.2337508. Epub 2024 May 26.
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.
脑胶质瘤是一种常见的颅内肿瘤，具有高度侵袭性和侵略性。丙酮酸激酶 M2（PKM2）在脑胶质瘤组织中过度表达。然而，PKM2 在脑胶质瘤中的生物学作用尚不清楚。
用 PKM2 shRNA 转染脑胶质瘤细胞，通过 qRT-PCR、CCK-8、Transwell、流式细胞术检测、Western blot 检测、ELISA 检测和丙酮酸激酶活性检测，探讨 PKM2 在脑胶质瘤进展中的作用。然后，利用 STRING 网站预测与 PKM2 相互作用的蛋白，并通过 Co-IP 实验进一步验证它们的相互作用。随后，再次进行上述实验，以寻找 CTNNB1 过表达对 PKM2 缺陷型脑胶质瘤细胞的影响。还建立了移植瘤模型，以进一步验证我们的发现。
PKM2 在脑胶质瘤细胞和组织中上调。抑制 PKM2 后，脑胶质瘤细胞的增殖、迁移、糖酵解和 EMT 明显减少，凋亡比例增加。STRING 网站的预测结果显示，CTNNB1 和 PKM2 具有最高的相互作用评分。Co-IP 实验进一步证实了 CTNNB1 和 PKM2 之间的相关性。PKM2 敲低抑制脑胶质瘤细胞增殖、迁移、糖酵解和 EMT，而 CTNNB1 过表达挽救了这些抑制作用。相应地，PKM2 敲低抑制了体内脑胶质瘤的生长。
综上所述，这些发现表明 PKM2 通过介导 CTNNB1 表达促进脑胶质瘤的进展，为脑胶质瘤的临床治疗提供了一个可能的分子标志物。
