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The effect of TFAP2A/ANXA8 axis on ferroptosis of cervical squamous cell carcinoma (CESC) in vitro

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Abstract

Potential role and associated mechanisms of Annexin A8 (ANXA8), a member of the Annexins family, in cervical squamous cell carcinoma (CESC) are still unclear, despite being upregulated in various malignant tumors. Here, we observed a notably elevated expression of ANXA8 in CESC cells. The inhibition of ANXA8 amplified the susceptibility of CESC cells to Erastin and sorafenib-induced ferroptosis, whereas it exerted minimal influence on DPI7 and DPI10-induced ferroptosis. The results from the Fe2+ concentration assay showed no significant correlation between ANXA8 gene knockdown and intracellular Fe2+ concentration induced by ferroptosis inducers. Western blot analysis demonstrated that the knockdown of ANXA8 did not alter ACSL4 and LPCAT levels under ferroptosis-inducing conditions, but it did result in a reduction in intracellular GSH levels induced by the ferroptosis inducer. Subsequently, we identified TFAP2A as an upstream transcription factor of ANXA8, which plays a role in regulating cell ferroptosis. The knockdown of TFAP2A significantly elevated MDA levels and depressed GSH levels in the presence of a ferroptosis inducer, thereby inhibiting cell ferroptosis. However, this inhibitory effect could be reversed by ANXA8 overexpression. Therefore, our research suggests that the TFAP2A/ANXA8 axis exerts regulatory control over ferroptosis in CESC cells by mediating GSH synthesis in System Xc.

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Data availability

The representative data are included in this article. The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

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Funding

This work was supported by the Medical Scientific Research Foundation of Zhejiang Province, Grant No. 2021KY338, 2023KY1066; Zhejiang Provincial Natural Science Foundation of China under Grant No. LY22H160010; Ningbo Natural Science Foundation, Project ID: 2021J318.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, 59 Liuting Street, Haishu District, Ningbo, Zhejiang, People’s Republic of China

    Yuehua Sheng, Huiqing Ding, Jiaqing Zhou, Yuejing Wu, Kejun Xu & Yongming Du

  2. Central Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China

    Fan Yang

  3. Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang, People’s Republic of China

    Fan Yang

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  1. Yuehua Sheng
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  2. Huiqing Ding
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  3. Jiaqing Zhou
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  4. Yuejing Wu
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  5. Kejun Xu
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  6. Fan Yang
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  7. Yongming Du
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Contributions

Yongming Du designed and performed the experiments. Yuehua Sheng wrote the manuscript. Yuehua Sheng and Huiqing Ding performed and analyzed experiments and prepared the figures. Yuehua Sheng, Huiqing Ding, Jiaqing Zhou, Yuejing Wu, Kejun Xu, Fan Yang performed experiments. Yongming Du guided the experiments. All authors have read and approved the final manuscript.

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Correspondence to Yongming Du.

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Sheng, Y., Ding, H., Zhou, J. et al. The effect of TFAP2A/ANXA8 axis on ferroptosis of cervical squamous cell carcinoma (CESC) in vitro. Cytotechnology (2024). https://doi.org/10.1007/s10616-024-00619-0

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