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EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A

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Abstract

Objective

Histone modification has a significant effect on gene expression. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme. The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors. The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis.

Methods

In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues, we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice. Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine (m6A) levels were modified.

Results

EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues. Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo. M6a regulation altered the effect of EZH2 on anoikis resistance.

Conclusion

Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification. Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

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Author notes

  1. The authors contributed equally to this study.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Shao-hai Wang, Lin Liu, Ke-yong Bao, Yi-fan Zhang, Wen-wen Wang, Shi Du, Jing Cai, Jian-feng Guo & Gang Lv

  2. Department of Obstetrics and Gynecology, Affiliated Hospital of Inner Mongolia University for The Nationalities, Tongliao, 028000, China

    Ke-yong Bao

  3. Department of Obstetrics and Gynecology, Bozhou Branch of Union Hospital, Bozhou, 833400, China

    Na-er Jia & Suo Suo

  4. Department of Obstetrics and Gynecology, Bozhou People’s Hospital, Bozhou, 833400, China

    Na-er Jia & Suo Suo

Authors
  1. Shao-hai Wang
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  2. Lin Liu
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  10. Jian-feng Guo
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Corresponding authors

Correspondence to Jian-feng Guo or Gang Lv.

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The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

Additional information

This study was funded by the National Natural Science Foundation of China (No. 81672573), Natural Science Foundation of Xinjiang Uygur Autonomous Region (No. 2021D01F21) and Natural Science Foundation of Hubei Province (No. 2021CFB474).

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Wang, Sh., Liu, L., Bao, Ky. et al. EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A. CURR MED SCI 43, 794–802 (2023). https://doi.org/10.1007/s11596-023-2719-4

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  • DOI: https://doi.org/10.1007/s11596-023-2719-4

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