HPV16激活自噬促进细胞增殖与迁移的分子机制研究

HPV16 infection can lead to condyloma acuminatum and cervical cancer, which is serious harm to women's health, but the pathogenesis is still not clear. Autophagy is an important regulatory mechanism in the growth, differentiation and death of eukaryotic cells, it is closely related to the development of disease. Genetic factors and epigenetic factors were all involved in autophagy regulation. In our previous studies, we demonstrated that HPV16 induces the activation of autophagy, and the lower methylation level in the promoter region of autophagy-related gene 10 (ATG10) and ATG12, which indicates that HPV16 activates autophagy promoting cell proliferation and migration through epigenetic modification. HPV16 activates autophagy, which may be the key link of disease progression. It is extremely important to confirm the molecular mechanism of this process. In the study, we will investigate the abnormal methylation sites of ATG10/12 caused by HPV16, and the structural protein of HPV16 involved in methylation regulation and autophagy activation. We will confirm that autophagy promotes cell proliferation and migration by regulating tumor microenviroment Lacking oxygen and nutrition , and the mediation Of ATG10/12. We will also analyze the promoting effect and mechanism of autophagy in disease progression, and discuss the feasibility of Autophagy - related genes used as early diagnosis and prognostic markers, to lay a theoretical foundation for the new method of clinical diagnosis and treatment.

HPV16感染可以导致尖锐湿疣和宫颈癌，严重危害女性健康，但其发病机制仍然不够明确。自噬是真核细胞生长、分化与死亡过程中重要的调控机制，与疾病发生发展密切相关；遗传因素与表观遗传因素异常均参与自噬调控。前期研究中我们发现HPV16+细胞中自噬被活化，自噬关键基因ATG10、ATG12甲基化水平降低，提示HPV16可能通过表观遗传修饰激活自噬来促进细胞的增殖与迁移，HPV16激活自噬可能是本病进展过程的中心环节，明确该过程的分子机制极其重要。课题拟进一步鉴定HPV16导致ATG10/12异常的甲基化位点、HPV16参与甲基化调控与自噬活化的结构蛋白，证实自噬通过调控缺氧与营养缺乏等微环境而促进细胞增殖与迁移，确证ATG10/12的重要介导作用，分析自噬在病程进展中的促进作用及其机制，探讨ATG10/12等自噬相关基因作为早期诊断、预后判断标志物的可行性，为临床诊治新方法奠定理论基础。

HPV16感染可以导致尖锐湿疣和宫颈癌，严重危害女性健康，但其发病机制仍然不够明确。自噬是真核细胞生长、分化与死亡过程中重要的调控机制，与疾病发生发展密切相关；遗传因素与表观遗传因素异常均参与自噬调控。我们发现HPV16+细胞中自噬被活化，自噬关键基因ATG10、ATG12甲基化水平降低，提示了HPV16可通过表观遗传修饰激活自噬来促进细胞的增殖与迁移，HPV16激活自噬是本病进展过程的重要环节。我们鉴定了HPV16感染导致ATG10/12异常的甲基化位点、HPV16参与甲基化调控与自噬活化的结构蛋白，证实了自噬通过调控缺氧与营养缺乏等微环境而促进细胞增殖与迁移，确证了ATG10/12的重要介导作用。研究结果提示了ATG10/12等自噬相关基因作为早期诊断、预后判断的标志物的可行性，该研究为探索临床HPV感染相关疾病诊治新方法奠定了理论基础。