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Knockdown of KDM2A inhibits proliferation associated with TGF-β expression in HEK293T cell

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Abstract

Lysine-specific demethylase 2A (KDM2A, also known as JHDM1A or FBXL11) plays an important role in regulating cell proliferation. However, the mechanisms on KDM2A controlling cell proliferation are varied among cell types, even controversial conclusions have been drawn. In order to elucidate the functions and underlying mechanisms for KDM2A controlling cell proliferation and apoptosis, we screened a KDM2A knockout HEK293T cell lines by CRISPR–Cas9 to illustrate the effects of KDM2A on both biological process. The results indicate that knocking down expression of KDM2A can significantly weaken HEK293T cell proliferation. The cell cycle analysis via flow cytometry demonstrate that knockdown expression of KDM2A will lead more cells arrested at G2/M phase. Through the RNA-seq analysis of the differential expressed genes between KDM2A knockdown HEK293T cells and wild type, we screened out that TGF-β pathway was significantly downregulated in KDM2A knockdown cells, which indicates that TGF-β signaling pathway might be the downstream target of KDM2A to regulate cell proliferation. When the KDM2A knockdown HEK293T cells were transient-transfected with KDM2A overexpression plasmid or treated by TGF-β agonist hydrochloride, the cell proliferation levels can be partial or completely rescued. However, the TGF-β inhibitor LY2109761 can significantly inhibit the KDM2A WT cells proliferation, but not the KDM2A knockdown HEK293T cells. Taken together, these findings suggested that KDM2A might be a key regulator of cell proliferation and cell cycle via impacting TGF-β signaling pathway.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (30900816 and 31371307) and the Fundamental Research Funds for the South-Central University for Nationalities (CZP17082).

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  1. Wen-hao Xu and Da-yan Liang contributed equally to this work.

Authors and Affiliations

  1. Institute for Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, 82 MinZu Ave., Wuhan, 430074, Hubei, People’s Republic of China

    Wen-hao Xu, Da-yan Liang, Qi Wang, Jinhua Shen, Qing-Hua Liu & Yong-Bo Peng

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  1. Wen-hao Xu
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  2. Da-yan Liang
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  3. Qi Wang
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Correspondence to Yong-Bo Peng.

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Xu, Wh., Liang, Dy., Wang, Q. et al. Knockdown of KDM2A inhibits proliferation associated with TGF-β expression in HEK293T cell. Mol Cell Biochem 456, 95–104 (2019). https://doi.org/10.1007/s11010-018-03493-5

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  • DOI: https://doi.org/10.1007/s11010-018-03493-5

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