基于外泌体miRNA途径探索中医湿热质容易罹患宫颈癌的分子机制

宫颈癌发病与高危型HPV感染密切相关，严重危害女性健康。中医“体病相关”理论为宫颈癌防治提供了新的思路和途径。我们前期研究发现中医湿热质是宫颈HPV感染、宫颈癌发生的危险因素，但其机制了解甚少。预实验显示：湿热质血浆及其外泌体均明显促进高危型HPV感染正常宫颈上皮细胞和宫颈癌细胞的生长，而且湿热质外泌体miR-4327亦能显著诱导上述细胞的生长和迁移。据此，推测外泌体miR-4327可能通过靶基因及其信号通路，促进高危型HPV感染正常宫颈上皮细胞发生癌变和宫颈癌细胞过度增殖与迁移，致使湿热质易发宫颈癌。本项目拟采用体内结合体外实验，围绕湿热质外泌体miR-4327，应用基因转染、RNA干扰、双荧光素酶报告基因等技术方法，明确湿热质外泌体miR-4327促进宫颈癌的发病过程，确定miR-4327的靶基因及其关键信号通路，阐明湿热质状态容易罹患宫颈癌的分子机制，将促进中医“治未病”健康工程。

Cervical cancer is closely associated with high-risk human papillomavirus (HR-HPV) infection, which seriously endangers women's health. The theory of “constitution-disease relation” in traditional Chinese medicine (TCM) provides a new perspective for the prevention and treatment of cervical cancer. Our previous study found that damp-heat constitution is a risk factor for cervical HPV infection and cervical cancer, but its mechanism is poorly understood. Our preliminary results showed that the plasma and exosomes of the population with damp-heat constitution significantly promoted the growth of normal cervical epithelial cells infected by HR-HPV and cervical cancer cells, and the exosome mir-4327 also significantly induced the growth and migration of cells above. Therefore, we speculated that exosome mir-4327 may promote the carcinogenesis of normal cervical epithelial cells infected with HR-HPV and the excessive proliferation and migration of cervical cancer cells through its target gene and signaling pathway, leading to the susceptibility of damp-heat constitution to cervical cancer. Our project intends to carry out in vitro and in vivo experiments around the exosomes mir-4327 of damp-heat constitution. Using gene transfection, RNA interference, dual luciferase reporter and other methods, we may determine whether the exosomes of damp-heat constitution can promote cervical carcinogenesis by mediating mir-4327, as well as target gene and key signal pathway of mir-4327, so as to clarify the mechanism on the susceptibility of damp-heat constitution to cervical cancer, which will promote the health engineering of the “preventive treatment of diseases” in TCM.