宫颈上皮内瘤变（CIN）及宫颈癌的发生进展是始于HPV感染的一个复杂、多步骤的过程，IFI16是机体应答外源性双链DNA病毒感染的重要免疫分子，课题组前期研究显示， IFI16在伴有HPV感染的宫颈炎、LSIL、HSIL中的表达依次升高，差异显著，可作为CIN的早期诊断及分级标记物。IFI16在宫颈癌组织中的表达则出现下调，沉默IFI16表达后癌细胞增殖和侵袭能力减弱，其表达与肿瘤分期分级肿瘤最大切面积负相关，以上提示IFI16在宫颈癌中发挥抑癌作用，但随着肿瘤进展出现降解。本课题拟明确下调癌组织内IFI16的核心作用蛋白和具体作用通路，预实验发现癌组织内TRIM31与IFI16呈负相关，TRIM31可能是下调IFI16关键蛋白之一。课题组将继续围绕IFI16展开深入研究，继续筛选出更多密切相关蛋白，更为系统的阐释IFI16的下调机制，为深入认识宫颈癌发生及进展机制提供新视角和治疗靶点。

The occurrence and development of cervical intraepithelial neoplasia（CIN） as well as cervical carcinoma is a complex and multi-step process that begins with HPV infection. IFI16 is an important immune molecule in response to exogenous double-stranded DNA virus infection and plays an important role in the innate immune response. Our previous studies have shown that the expression of IFI16 has significantly increased from cervical inflammatory lesions to low-grade and high-grade intraepithelial neoplasia with HPV infection. Compared with P16, the widely used molecular biology marker, IFI16 has stronger specificity and can be used as a molecular marker in early pathological diagnosis and classification of CIN, which can help timely treatment and prevent malignant progression of the disease. Another important finding in our study is that the expression of IFI16 is unexpectedly down-regulated in cervical cancer tissues After silencing the expression of IFI16, the proliferation and invasiveness of cervical carcinoma cells were significantly reduced. The expression of IFI16 was negatively correlated with the stage and grading of cervical carcinoma and the maximum tumor area. These results suggested that IFI16 plays an anti-cancer role in cervical carcinoma, but it degrades with the progression of cervical carcinoma. The purpose of our project is to identify the core proteins and specific pathways of down-regulation of IFI16 protein expression in cervical carcinoma tissues. Our preliminary experiments have found that TRIM31 is associated with IFI16 in cervical carcinoma tissues. The up-regulation of TRIM31 expression is negatively correlated with IFI16. TRIM31 may be one of the key proteins of down-regulation of IFI16. We will continue to screen more closely related proteins which can correlated with IFI16, and explain the down-regulation mechanism of IFI16 in cervical carcinoma more systematically. Our study is to provide a new integrated perspective and new insights for better understanding of development of cervical carcinoma with HPV infection.