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Exosomal circCARM1 from spheroids reprograms cell metabolism by regulating PFKFB2 in breast cancer

Oncogene volume 41, pages 2012–2025 (2022)Cite this article

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A Correction to this article was published on 22 February 2022

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Abstract

Cancer stem cells (CSC) are the major obstacle for cancer therapy in clinic. Exosomes are one type of vesicles that containing circular RNA (circRNAs) involved in cell–cell communication. However, the roles of breast CSC (BCSC) exosomes are still unclear, and the purpose of the study was to investigate breast cancer cell metabolism reprogramming by circRNAs from BCSC exosomes. The circRNA array was performed in the exosomes secreted from spheroids of MDA-231 cells. circCARM1 was higher in BCSC exosomes than it in the parent breast cancer cells. Further investigation demonstrated that BCSC exosomes circCARM1 played an important role in breast cancer cell glycolysis by miR-1252-5p/PFKFB2. In a conclusion, BCSC exosome-derived circCARM1 played an important role in breast cancer cell glycolysis by sponging miR-1252-5p which regulated PFKFB2 expression.

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Fig. 1: BCSC exosomes mediated breast cancer cell glycolysis.
Fig. 2: CircRNA profile of the exosomes from BCSC.
Fig. 3: Identification the circular RNA structure and clinical features of circCARM1.
Fig. 4: CircCARM1 from CSC exosomes of spheroids increased aerobic glycolysis.
Fig. 5: EIF4A3-regulated circCARM1 expression in breast cancer cells.
Fig. 6: CircCARM1 bond to miR-1252-5p in breast cancer cells.
Fig. 7: CircCARM1 regulated PFKFB2 expression via miR-1252-5p in breast cancer cells.
Fig. 8: PFKFB2 partially rescued the effect of exosomal circCARM1 on cancer cell glycolysis.
Fig. 9: Biological implications of circCARM1 in breast cancer in vivo.
Fig. 10: A schematic diagram of the mechanism.

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Acknowledgements

This study was supported by Shanghai Municipal Health Commission (No: 202140454), Shanghai Science and Technology Committee (No: 19140901000), and National Natural Science Foundation of China (No: 81502571).

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Author notes

  1. These authors contributed equally: Li Ma, Fanli Hua.

Authors and Affiliations

  1. Medical Research Center, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China

    Yonglei Liu & Li Ma

  2. Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China

    Fanli Hua

  3. Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China

    Zhihui Min & Wei Zhang

  4. Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China

    Yanxia Zhan

  5. Department of Pathology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China

    Junxia Yao

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  1. Yonglei Liu
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  4. Zhihui Min
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Contributions

YL was responsible for experimental design, financial support, and having done most of experiments. LM, YZ, and ZM were responsible for conducting a part of experiments. WZ was responsible for specimen collection. FH was responsible for data analysis. JY was responsible for pathological associated data analysis.

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Correspondence to Yonglei Liu.

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Liu, Y., Ma, L., Hua, F. et al. Exosomal circCARM1 from spheroids reprograms cell metabolism by regulating PFKFB2 in breast cancer. Oncogene 41, 2012–2025 (2022). https://doi.org/10.1038/s41388-021-02061-4

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