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TRIM28 recruits E2F1 to regulate CBX8-mediated cell proliferation and tumor metastasis of ovarian cancer

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Abstract

Chromobox protein homolog 8 (CBX8) is a transcriptional suppressor participated in various cancers. However, the function and mechanism of CBX8 in the progression of ovarian cancer (OC) are unclear. In this study, we found that CBX8 was upregulated in OC tissues originating from GEPIA and TNM databases, OC patients’ samples from hospital, and OC cell lines. Furthermore, CBX8 knockdown by short hairpin RNA (shRNA) technology markedly inhibited proliferation and invasion, induced migration, cell cycle arrest, and apoptosis in vitro. Mechanistically, CBX8 activated PI3K/AKT/mTOR signaling pathway to take effect. In addition, TRIM28 and E2F1 were enriched in OC tissues from the TNM database and OC patients’ samples similar to the results of CBX8. Correlation analysis indicated positive correlations among TRIM28, E2F1, and CBX8. E2F1 was proved to bind to the promoter regions of CBX8 and TRIM28, while TRIM28 recruited E2F1 to increase the expression of CBX8 to further increase cell viability, proliferation, and invasion, and decrease migration, apoptosis, and cell cycle progression. Finally, CBX8 or TRIM28 knockdown repressed tumor growth and metastasis of OC in vivo. Therefore, our study showed that the promoting effect of CBX8 on tumor growth and metastasis of OC was participated in the PI3K/AKT/mTOR signaling, TRIM28 and E2F1. Our findings suggested that CBX8 could serve as a potential marker and therapeutic target for OC patients.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 82071630 and 81771560), Construction of Key Disciplines of Tongji Hospital in the Fifth cycle (No. ZD16-FC-1), Clinical Research Fund of Zhejiang Medical Association (No. 2021ZYC-A106), Science and Technology Programs of Ningbo (No. 202003N4289), the Medical and Health Science and Technology Program of Zhejiang Province, China No. 2021440659) and Research and application based on evidence-based medicine in improving female ovarian function with traditional Chinese medicine (No 0.2022Z148).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China

    Fubin Zhang, Chenghao Wu, Dongsheng Shen & Xiaowen Tong

  2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, 315010, Zhejiang Province, China

    Fubin Zhang, Tianhong Zhu, Lixiao Liu, Yutao Guan & Huiqing Ding

  3. Department of Traditional Medicine, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, 315010, Zhejiang Province, China

    Xueqin Chen

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  1. Fubin Zhang
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Contributions

FZ, YG, HD, and XT: designed the study and carried them out, FZ, TZ, CW, DS, LL, and XC: supervised the data collection, analyzed the data, interpreted the data, FZ, YG, HD, and XT: prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

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Correspondence to Yutao Guan, Huiqing Ding or Xiaowen Tong.

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Ethical approval involved human participants was obtained from the Ethics Committee of The First Affiliated Hospital of Ningbo University (Approval no. NBU-2023-085). All animal experiments were authorized by the Laboratory Animal Ethical and Welfare Committee of Tongji University School of Medicine (Approval no. 2023-05-0A), and performed in accordance with Laboratory Animal-Guideline for ethical review of animal welfare of People’s Republic of China National Standard (GB/T 35892-2018).

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Zhang, F., Zhu, T., Wu, C. et al. TRIM28 recruits E2F1 to regulate CBX8-mediated cell proliferation and tumor metastasis of ovarian cancer. Human Cell 36, 2113–2128 (2023). https://doi.org/10.1007/s13577-023-00983-7

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