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

Fubin Zhang; Tianhong Zhu; Chenghao Wu; Dongsheng Shen; Lixiao Liu; Xueqin Chen; Yutao Guan; Huiqing Ding; Xiaowen Tong

doi:10.1007/s13577-023-00983-7

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

Hum Cell. 2023 Nov;36(6):2113-2128. doi: 10.1007/s13577-023-00983-7. Epub 2023 Sep 14.

Authors

Fubin Zhang^{1

2}, Tianhong Zhu², Chenghao Wu¹, Dongsheng Shen¹, Lixiao Liu², Xueqin Chen³, Yutao Guan⁴, Huiqing Ding⁵, Xiaowen Tong⁶

Affiliations

¹ Department of Obstetrics and Gynecology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China.
² Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, 315010, Zhejiang Province, China.
³ Department of Traditional Medicine, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, 315010, Zhejiang Province, China.
⁴ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, 315010, Zhejiang Province, China. 2309732100@qq.com.
⁵ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, 315010, Zhejiang Province, China. dinghuiqing@nbdyyy.com.
⁶ Department of Obstetrics and Gynecology, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, China. tongxiaowen2022@163.com.

PMID: 37709991
DOI: 10.1007/s13577-023-00983-7

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.

Keywords: CBX8; Ovarian cancer; PI3K/AKT/mTOR; Proliferation; TRIM28.

Abstract

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