PKM2 promotes glioma progression by mediating CTNNB1 expression.

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Neurological Research Pub Date : 2024-07-01 Epub Date: 2024-05-26 DOI:10.1080/01616412.2024.2337508

Chunyang Ma, Yuan Feng, Kaiyi Zhong, Jiali Wei

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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PKM2 通过介导 CTNNB1 的表达促进胶质瘤的进展。

背景：胶质瘤是一种常见的颅内肿瘤，具有高度侵袭性和侵袭性。丙酮酸激酶 M2（PKM2）在胶质瘤组织中过度表达。然而，PKM2在胶质瘤中的生物学作用尚不清楚：方法：对转染PKM2 shRNA的胶质瘤细胞进行qRT-PCR、CCK-8、Transwell、流式细胞术检测、Western印迹检测、ELISA检测和丙酮酸激酶活性检测，以探讨PKM2在胶质瘤进展中的功能。然后，利用STRING网站预测了与PKM2相互作用的蛋白，并通过Co-IP实验进一步验证了它们之间的相互作用。随后，研究人员再次进行了上述实验，以寻找catenin beta 1（CTNNB1）过表达对PKM2缺陷胶质瘤细胞的影响。为了进一步验证我们的发现，我们还建立了移植肿瘤模型：结果：PKM2在胶质瘤细胞和组织中上调。结果：PKM2在胶质瘤细胞和组织中上调，抑制PKM2后，胶质瘤细胞的增殖、迁移、糖酵解和EMT显著降低，凋亡比例增加。STRING网站的预测结果显示，CTNNB1与PKM2的相互作用得分最高。CTNNB1和PKM2之间的相关性在Co-IP测试中得到了进一步证实。PKM2敲除抑制了胶质瘤细胞的增殖、迁移、糖酵解和EMT，而CTNNB1的过表达则挽救了这些抑制作用。相应地，PKM2敲除抑制了胶质瘤在体内的生长：总之，这些研究结果表明，PKM2通过介导CTNNB1的表达来促进胶质瘤的进展，为胶质瘤的临床治疗提供了一个可能的分子标记。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Research 医学-临床神经学

CiteScore

3.60

自引率

0.00%

发文量

116

审稿时长

5.3 months

期刊介绍： Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.