背景：宫颈癌（CC）对全球女性健康构成重大威胁，高危人乳头瘤病毒是主要病因。 DNA 损伤修复 (DDR) 蛋白拓扑异构酶 I (TOP1) 与多种癌症有关，但其在 CC 中的独特作用和机制尚未完全阐明。方法：我们利用 qRT-PCR 和 IHC 研究了宫颈上皮内瘤变 (CIN) 和 CC 组织中的 TOP1 表达，将结果与患者预后相关联。随后在体外和体内进行了敲低研究，以评估 TOP1 对肿瘤生长、DNA 修复和炎症反应的影响。结果：TOP1在CIN和CC中高表达，与患者预后呈负相关。 TOP1 的抑制会阻碍 CC 细胞生长并破坏 DNA 修复。 TOP1 被证明能够以 cGAS 依赖性方式调节肿瘤促进炎症和程序性死亡配体 1 (PD-L1) 的产生。 HPV 癌蛋白 E6 和 E7 上调 TOP1 并激活 cGAS-PD-L1 通路。结论：TOP1 作为 DNA 修复介质，促进 CC 的发展和免疫逃避。靶向 TOP1-cGAS-PD-L1 轴可能是 CC 的潜在治疗策略。版权所有 © 2024 Luo、Niu、Liu、Zhang、Deng、Mu、Xu 和 Hong。

Background: Cervical cancer (CC) stands as a significant health threat to women globally, with high-risk human papillomaviruses as major etiologic agents. The DNA damage repair (DDR) protein topoisomerase I (TOP1) has been linked to various cancers, yet its distinct roles and mechanisms in CC are not fully elucidated. Methods: We investigated TOP1 expression in cervical intraepithelial neoplasia (CIN) and CC tissues utilizing qRT-PCR and IHC, correlating findings with patient prognosis. Subsequent knockdown studies were performed in vitro and in vivo to evaluate the influence of TOP1 on tumor growth, DNA repair, and inflammatory responses. Results: TOP1 was highly expressed in CIN and CC, negatively correlating with patient prognosis. Inhibition of TOP1 impeded CC cell growth and disrupted DNA repair. TOP1 was shown to regulate tumor-promoting inflammation and programmed death-ligand 1 (PD-L1) production in a cGAS-dependent manner. HPV oncoproteins E6 and E7 upregulated TOP1 and activated the cGAS-PD-L1 pathway. Conclusions: TOP1 acts as a DNA repair mediator, promoting CC development and immune evasion. Targeting the TOP1-cGAS-PD-L1 axis could be a potential therapeutic strategy for CC.Copyright © 2024 Luo, Niu, Liu, Zhang, Deng, Mu, Xu and Hong.