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Neurological Research
A Journal of Progress in Neurosurgery, Neurology and Neurosciences
Volume 46, 2024 - Issue 7
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Research Article

PKM2 promotes glioma progression by mediating CTNNB1 expression

, , &
Pages 583-592 | Received 25 Jun 2023, Accepted 26 Mar 2024, Published online: 26 May 2024
 

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.

Acknowledgments

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Abbreviation

Co-IP=

co-immunoprecipitation

CTNNB1=

catenin beta 1

ELISA=

enzyme-linked immunosorbent assay

EMT=

epithelial-mesenchymal transition

GBM=

glioblastoma

IHC=

immunohistochemistry

NHAs=

human astrocytes

OS=

overall survival

PKM2=

pyruvate kinase M2

qRT-PCR=

quantitative real-time PCR

WB=

western blot

Authors’ contribution

CYM and YF conceived the experimental design, provided supervision during the research, and proofread the article. KYZ and JLW performed all experimental work, statistical analyses and wrote the manuscript.

Additional information

Funding

This work is supported by Natural Science Foundation of China (82160135, 82360146), Hainan key research and development projects (ZDYF2022SHFZ016, Hainan Provincial Natural Science Foundation High Level Talent Project (821RC705), Hainan Province Clinical Medical Center, Hainan Provincial Natural Science Foundation (No. 822QN455, 821MS0825), Hainan Provincial Health Science and Technology Innovation joint project of China (SQ2023WSJK0153), National Natural Science Foundation of China Cultivation 530 Project (Youth project) (2021QNXM12,13,17), National Natural Science Foundation of China Cultivation 530 Project (General Program) (2021MSXM17).

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