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DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells

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Abstract

Background

Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated.

Methods and results

DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling key proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells.

Conclusions

Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.

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Data availability

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

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Funding

This work was funded by the Natural Scientific Foundation of China (Project No. 81760473) and Science and Technology Plan Project of the Health Commission of Jiangxi Province (Project No. 20195498).

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Authors and Affiliations

  1. Department of Gynecological Oncology, Maternal and Child Health Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China

    Qi-Zhou Zhu & Zhong-Qing Xiao

  2. The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, People’s Republic of China

    Hao-Yue Liu, Xiao-Yan Zhao, Le-Jia Qiu, Ting-Ting Zhou, Xue-Ying Wang & He-Ping Chen

  3. Department of Gynecological Oncology, JiangXi Maternal and Child Health Hospital, Nanchang, 330006, People’s Republic of China

    Qi-Zhou Zhu & Zhong-Qing Xiao

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  1. Qi-Zhou Zhu
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Contributions

QZZ: Protocol development, data collection, data analysis, and manuscript writing. HYL: Data collection, data analysis, and manuscript writing. XYZ, LJQ, TTZ, and XYW: Data collection. HPC and ZQX: Project development, manuscript editing. All authors approved final manuscript.

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Correspondence to Zhong-Qing Xiao.

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Zhu, QZ., Liu, HY., Zhao, XY. et al. DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells. Mol Biol Rep 48, 6075–6083 (2021). https://doi.org/10.1007/s11033-021-06614-4

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