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JMJD5 inhibits lung cancer progression by regulating glucose metabolism through the p53/TIGAR pathway

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Abstract

Metabolic reprogramming is considered one of the main driving forces for tumor progression, providing energy and substrates of biosynthesis to support rapid neoplastic proliferation. Particularly, the tumor suppressor protein p53 was shown to revert the Warburg effect and play complex roles in regulating glucose metabolism. Jumonji C domain-containing protein 5 (JMJD5) has previously been reported as a negative regulator of p53. However, the role of JMJD5 in p53-mediated metabolic reprogramming remains elusive. Here, we discovered that knockdown of JMJD5 significantly enhances TIGAR expression in p53 wild-type non-small cell lung cancer (NSCLC) cells, which could further suppress glycolysis and promote the pentose phosphate pathway. Besides, JMJD5 knockdown promotes the NSCLC cell proliferation in vitro and xenograft tumor growth in vivo, while silencing TIGAR can abolish this effect. Low JMJD5 expression levels are associated with elevated TIGAR levels and correlates with poor prognosis in lung cancer patients. Taken together, our findings suggest that JMJD5 is a key regulator of tumor glucose metabolism by targeting the p53/TIGAR metabolic pathway.

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Data availability

All the datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Zhejiang Provincial Natural Science Foundation of China (LY20H160040 and LY18H160024) and the National Natural Science Foundation of China (81772919).

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Authors and Affiliations

  1. Department of Pathology and Pathophysiology, and Department of Medical Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Guiling Liu & Jing Shen

  2. Department of Pathology and Pathophysiology, and Department of Radiation Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Hongyan Qi

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Contributions

All authors have contributed to this study. SJ, QH, LG: experimental design, material preparation, data collection and analysis; SJ, LG: writing the first draft of the manuscript; SJ: funding acquisition. All authors commented on previous versions, and read and approved the final manuscript.

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Correspondence to Jing Shen.

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Liu, G., Qi, H. & Shen, J. JMJD5 inhibits lung cancer progression by regulating glucose metabolism through the p53/TIGAR pathway. Med Oncol 40, 145 (2023). https://doi.org/10.1007/s12032-023-02016-7

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