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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1450875
This article is part of the Research Topic Novel Biomarkers in Solid Tumors and Related Medicine Therapy View all 4 articles

Oncoproteins E6 and E7 upregulate topoisomerase I to activate the cGAS-PD-L1 pathway in cervical cancer development

Provisionally accepted
Ying Luo Ying Luo 1Mengda Niu Mengda Niu 1Yanfei Liu Yanfei Liu 1Miaochang Zhang Miaochang Zhang 1Yuanyuan Deng Yuanyuan Deng 1Dan Mu Dan Mu 1Junfen Xu Junfen Xu 2*Shiyuan` Hong Shiyuan` Hong 1*
  • 1 Institute of Life Sciences, Chongqing Medical University, Chongqing, China
  • 2 Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Cervical cancer (CC) ranks as the fourth most lethal cancer among women worldwide. The DNA damage repair (DDR) protein topoisomerase I (TOP1) plays a crucial role in maintaining genomic stability and has been implicated in various cancers. However, its specific functions and mechanisms in CC remain unclear. In this study, we found that TOP1 was highly expressed in cervical intraepithelial neoplasia (CIN) and CC tissues. Elevated TOP1 expression is negatively correlated with the prognosis of CC patients. Inhibition of TOP1 suppresses CC cell growth and impairs DNA repair both in vitro and in vivo. Furthermore, TOP1 is responsible for the production of programmed death-ligand 1 (PD-L1) in a cyclic GMP-AMP synthase (cGAS)-dependent manner. Silencing TOP1 reduces the expression of cGAS and PD-L1. Additionally, TOP1 co-localizes with cGAS in CC cells. Human papillomavirus oncoproteins E6 and E7 significantly upregulate TOP1 and activate the non-canonical cGAS-PD-L1 pathway to promote CC development. Our findings suggest that the TOP1-cGAS-PD-L1 signaling axis could be a promising therapeutic target for CC.

    Keywords: DDR, TOP1, CGAS, PD-L1, Human papillomavirus, cervical cancer

    Received: 18 Jun 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Luo, Niu, Liu, Zhang, Deng, Mu, Xu and Hong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Junfen Xu, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
    Shiyuan` Hong, Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China

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