Liao Yaqi, Chen Ranzhong, Tang Erqun, Tang Shuangyang
Institute of pathogenic Biology Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, School of Basic Medicine Sciences, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, China; Department of Clinical Laboratory, Hanshou People's Hospital, Changde, 415900, Hunan, China.
Institute of pathogenic Biology Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, School of Basic Medicine Sciences, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, China.
Microb Pathog. 2025 Sep;206:107849. doi: 10.1016/j.micpath.2025.107849. Epub 2025 Jun 28.
As a common pathogen of sexually transmitted diseases, Chlamydia trachomatis (C. trachomatis) may be a cofactor in the progression of cervical cancer induced by persistent HPV infection, but its molecular mechanism is unclear. The aim of this study is to explore whether HPV16 E6 and C. trachomatis Pgp3 proteins inhibit apoptosis through the Daxx-mediated MDM2-p53 pathway, in order to reveal the potential mechanism of their synergistic effects.
The HeLa cell model was used to analyze the effects of HPV16 E6 and Pgp3 proteins on Daxx expression and the MDM2-p53 pathway, combined with interfering with Daxx, TNF-α-induced apoptosis assay and Nutlin-3a treatment to validate the function of key molecules.
HPV16 E6 and C. trachomatis Pgp3 proteins can upregulate the expression of Daxx proteins individually or synergistically, and the inhibitory on TNF-α-induced apoptosis may be superimposed. Interference with Daxx partially reversed the apoptosis inhibition of HPV16 E6 and Pgp3, suggesting that it may act by promoting MDM2 phosphorylation and p53 degradation. Moreover, Nutlin-3a treatment can attenuate the apoptosis inhibitory of HPV16 E6 and Pgp3, further supporting the involvement of MDM2-p53 pathway.
This study suggests that HPV16 E6 and C. trachomatis Pgp3 proteins can inhibit TNF-α-induced apoptosis through Daxx-mediated MDM2-p53 pathway, which may provide a mechanistic foundation for the study of HPV16 and C. trachomatis co-infection on cervical cancer progression.
沙眼衣原体（C. trachomatis）作为性传播疾病的常见病原体，可能是持续性人乳头瘤病毒（HPV）感染所致宫颈癌进展的一个辅助因素，但其分子机制尚不清楚。本研究旨在探讨HPV16 E6蛋白和沙眼衣原体Pgp3蛋白是否通过Daxx介导的MDM2-p53途径抑制细胞凋亡，以揭示它们协同作用的潜在机制。
利用HeLa细胞模型分析HPV16 E6蛋白和Pgp3蛋白对Daxx表达及MDM2-p53途径的影响，并结合干扰Daxx、肿瘤坏死因子-α（TNF-α）诱导的细胞凋亡检测以及Nutlin-3a处理来验证关键分子的功能。
HPV16 E6蛋白和沙眼衣原体Pgp3蛋白可单独或协同上调Daxx蛋白的表达，且对TNF-α诱导的细胞凋亡的抑制作用可能会叠加。干扰Daxx可部分逆转HPV16 E6蛋白和Pgp3蛋白对细胞凋亡的抑制作用，提示其可能通过促进MDM2磷酸化和p53降解发挥作用。此外，Nutlin-3a处理可减弱HPV16 E6蛋白和Pgp3蛋白对细胞凋亡的抑制作用，进一步支持MDM2-p53途径的参与。
本研究表明，HPV16 E6蛋白和沙眼衣原体Pgp3蛋白可通过Daxx介导的MDM2-p53途径抑制TNF-α诱导的细胞凋亡，这可能为研究HPV16与沙眼衣原体共同感染对宫颈癌进展的影响提供机制基础。
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