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Extracellular Vesicles Derived from Glioma Stem Cells Affect Glycometabolic Reprogramming of Glioma Cells Through the miR-10b-5p/PTEN/PI3K/Akt Pathway

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Abstract

Objective

Glioma is one of the most prevalently diagnosed types of primary malignant brain tumors. Glioma stem cells (GSCs) are crucial in glioma recurrence. This study aims to elucidate the mechanism by which extracellular vehicles (EVs) derived from GSCs modulate glycometabolic reprogramming in glioma.

Methods

Xenograft mouse models and cell models of glioma were established and treated with GSC-EVs. Additionally, levels and activities of PFK1, LDHA, and FASN were assessed to evaluate the effect of GSC-EVs on glycometabolic reprogramming in glioma. Glioma cell proliferation, invasion, and migration were evaluated using MTT, EdU, Colony formation, and Transwell assays. miR-10b-5p expression was determined, with its target gene PTEN and downstream pathway PI3K/Akt evaluated. The involvement of miR-10b-5p and the PI3K/Akt pathway in the effect of GSC-EVs on glycometabolic reprogramming was tested through joint experiments.

Results

GSC-EVs facilitated glycometabolic reprogramming in glioma mice, along with enhancing glucose uptake, lactate level, and adenosine monophosphate-to-adenosine triphosphate ratio. Moreover, GSC-EV treatment potentiated glioma cell proliferation, invasion, and migration, reinforced cell resistance to temozolomide, and raised levels and activities of PFK1, LDHA, and FASN. miR-10b-5p was highly-expressed in GSC-EV-treated glioma cells while being carried into glioma cells by GSC-EVs. miR-10b-5p targeted PTEN and activated the PI3K/Akt pathway, hence stimulating glycometabolic reprogramming.

Conclusion

GSC-EVs target PTEN and activate the PI3K/Akt pathway through carrying miR-10b-5p, subsequently accelerating glycometabolic reprogramming in glioma, which might provide new insights into glioma treatment.

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Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all the participants involved in this study. This study was funded by the Affiliated Hospital of North Sichuan Medical College of China (2019ZD001) the North Sichuan Medical College (CBY23-ZDA01) and the Bureau of Science and Technology Nanchong City (19SXHZ0321).

Funding

Thia studies was funded by the Affiliated Hospital of North Sichuan Medical College of China (2019ZD001), the North Sichuan Medical College (CBY23-ZDA01) and the Bureau of Science and Technology Nanchong City (19SXHZ0321).

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  1. Department of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China

    Shun Li, Lifang Mao, Lvmeng Song, Xiaochao Xia, Zihao Wang, Yinchuan Cheng & Xiaoping Tang

  2. Neurosurgical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China

    Shun Li & Xiaoping Tang

  3. Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China

    Shun Li

  4. Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, 362000, Fujian, China

    Jinqing Lai & Xiangrong Chen

Authors
  1. Shun Li
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  2. Lifang Mao
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  3. Lvmeng Song
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  4. Xiaochao Xia
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  5. Zihao Wang
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  6. Yinchuan Cheng
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  7. Jinqing Lai
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  8. Xiaoping Tang
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  9. Xiangrong Chen
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Contributions

Study concepts and manuscript review: Shun Li, Lifang Mao, and Lvmeng Song; Study design and manuscript preparation: Shun Li, Lifang Mao, and Lvmeng Song; Definition of intellectual content and manuscript editing: Xiaoping Tang and Xiangrong Chen; Experimental studies and data acquisition: Shun Li, Lifang Mao, and Xiaochao Xia; Data analysis: Zihao Wang, Yinchuan Cheng and Jinqing Lai. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shun Li, Xiaoping Tang or Xiangrong Chen.

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Ethics Approval and Consent to Participate

Approval was obtained from the ethics committee of Affiliated Hospital of North Sichuan Medical College. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Not applicable.

Competing Interests

The authors have no competing interests to declare that are relevant to the content of this article.

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Shun Li, Lifang Mao and Lvmeng Song are co-first authors and contributed equally to this article.

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Li, S., Mao, L., Song, L. et al. Extracellular Vesicles Derived from Glioma Stem Cells Affect Glycometabolic Reprogramming of Glioma Cells Through the miR-10b-5p/PTEN/PI3K/Akt Pathway. Stem Cell Rev and Rep 20, 779–796 (2024). https://doi.org/10.1007/s12015-024-10677-8

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  • DOI: https://doi.org/10.1007/s12015-024-10677-8

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