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KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner

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Abstract

Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial–mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.

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Acknowledgements

This study was supported by Beijing Natural Science Foundation (Grant No. 7192014); the Open Project of Key Laboratory of Genomics and Precision Medicine, Chinese Academy of Sciences; the National Laboratory of Biomacromolecules (Grant No. 2017kf02); National Natural Sciences Foundation of China (Grant No. 30800580).

Funding

Funding was provided by Beijing Municipal Natural Science Foundation (Grant No. 7192014).

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Authors and Affiliations

  1. Faculty of Environment and Life, Beijing University of Technology, Pingleyuan 100#, District of Chaoyang, Beijing, 100124, China

    Xin-Yu Wang, Hong-Ming Li, Ran Xia, Xiang Li, Xing Zhang, Tong-Zhao Jin & Hong-Sheng Zhang

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  1. Xin-Yu Wang
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Contributions

The research was supervised by ZHS. The research conducted by WXY and LHM. Interpretation of the data were done by XR, LX, ZX and JTZ. Funding was exquisite by ZHS. Writing and reviewing of manuscript were performed by WXY and ZHS and edited by ZHS.

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Correspondence to Hong-Sheng Zhang.

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Wang, XY., Li, HM., Xia, R. et al. KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner. Mol Cell Biochem 479, 915–928 (2024). https://doi.org/10.1007/s11010-023-04777-1

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