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Role of ZNF334 in cervical cancer: implications for EMT reversal and tumor suppression

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Abstract

Zinc-finger proteins are involved in many biological processes. However, the role of Zinc-finger protein 334 (ZNF334) in cervical cancer remains unidentified. This study showed that promoter methylation of ZNF334 was responsible for its reduced expression. ZNF334 suppressed malignant biological behaviors in cervical cancer. Notably, ZNF334 reversed the EMT process both in vitro and in vivo. RNA-seq coupled with bioinformatics analysis caught P3H3 which is upregulated by ZNF334. Dual-luciferase reporter and Chromatin immunoprecipitation assays illustrated that ZNF334 directly regulate P3H3. Knockdown of P3H3 attenuated the reversal of EMT induced by ZNF334. Additionally, ZNF334 overexpression sensitized cervical cancer cells to the cytotoxic effects of paclitaxel, cyclosporine and sunitinib. In conclusions, this study illustrated that DNA methylation-based silencing ZNF334 played a vital role in cervical cancer, by regulating P3H3 in turn affects EMT. ZNF334 has the potential to become a novel diagnostic biomarker and a potential treatment target for cervical cancer.

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Data availability

Online analysis was performed using UALCAN (http://ualcan.path.uab.edu), CTD (https://ctdbase.org), STRING (https://cn.string-db.org) and Gepia2 (http://gepia2.cancer-pku.cn) with TCGA database. Part of data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

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Acknowledgements

Not applicable.

Funding

This study was supported by National Natural Science Foundation of China (#82172619), Natural Science Foundation of Chongqing (CSTC2021jscx-gksb-N0023, CSTB2022NSCQ-M SX0063, CSTB2023NSCQ-MSX0386) and Medical and Industrial Integration Project (2022CDJYGRH-002).

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Author notes

  1. Qian Li and Xiangyi Zhou have contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Qian Li, Xiangyi Zhou, Yijia Gong, Bianfei Shao, Jianhua Wang, Lijuan Zhao, Qi Xiong, Yue Wu, Jun Tang, Qiyu Yang, Junying Tang & Tingxiu Xiang

  2. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China

    Qian Li & Tingxiu Xiang

  3. West China School of Medicine, Sichuan University, Chengdu Sichuan, 610065, China

    Jiayi Xiao

  4. Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

    Xue Gong

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Contributions

TX, JT: conception and design. QL, XZ: performed majority of experiments. YG, BS, JW, LZ, QX: performed experiments and analyzed data. YW, JT: collected samples. QL: drafted the manuscript. JX, XG: reviewed data and manuscript. TX, QL,JT: reviewed data and finalized the manuscript. All authors reviewed and approved the final version.

Corresponding authors

Correspondence to Junying Tang or Tingxiu Xiang.

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The authors declare no competing interests.

Institutional Review Board

Clinical samples used were subjected to histological diagnosis by pathologists, and informed consent was obtained from patients for the acquisition of tissue specimens. The Ethics Committee of Chongqing University Cancer Hospital approved of this study (approval notice: CZLS2022030-A). All animal experiment finished in Laboratory Animal Center of Chongqing University Cancer Hospital (CQCH-LAE-A0000202010).

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Informed consent was obtained from all subjects involved in the study.

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Li, Q., Zhou, X., Xiao, J. et al. Role of ZNF334 in cervical cancer: implications for EMT reversal and tumor suppression. Med Oncol 41, 191 (2024). https://doi.org/10.1007/s12032-024-02433-2

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