高危型HPV感染可导致抑癌基因甲基化异常，诱导宫颈癌发生。有研究报道HPV16 E6能抑制p53的活性，且p53是TET1潜在的作用靶点之一。但目前TET1在病毒相关肿瘤发生中的作用及机制尚未被阐明，只知道其与多种肿瘤的发生密切相关。我们前期的研究证实TET1与宫颈癌细胞恶性生物学行为有关，具有抑癌作用；且TET1可以调控宫颈癌细胞中p53表达；并发现干扰宫颈癌细胞HPV16 E6表达，可以使TET1表达升高，提示二者之间存在相互作用。因而推测：HPV16通过E6蛋白抑制TET1表达，上调p53的甲基化水平，导致p53抑癌活性被抑制，从而促进宫颈癌的发生发展。为此，我们拟从组织、细胞和动物水平，采用荧光素酶报告系统、ChIP及CRISPR/Cas9打靶技术，解析TET1在HPV16 E6诱导宫颈癌变过程中的作用及相关机制。该研究对子宫颈癌早期预警及提出新的治疗方案具有重要意义。

High-risk HPV infection can lead to the methylation abnormality of several tumor suppressor genes and induce the occurrence of cervical cancer. TET1 is a newly discovered DNA demethyltransferase, which is closely related to the development of various tumors.However, the role and mechanism of TET1 in viral tumor induction have not been elucidated. Our previous study found that TET1 is closely related to the malignant biological behavior of cervical cancer cells and plays a role in inhibiting cancer. Interference with the expression of HPV16 E6 could increase the expression of TET1, which suggested that HPV16 E6 can regulate the TET1 gene in cervical cancer cells. In addition, HPV 16 E6 protein has been reported to inhibit p53 activity, and p53 is a potential target of TET1. We also found that TET1 could regulate p53 in cervical cancer cells. Thus we speculate that HPV 16 may inhibit the expression of TET1 gene through E6 protein, thus changing the methylation status of p53, and then inhibiting the anti-cancer activity of p53 and promoting the development of cervical cancer. This study will analyze the role and mechanism of TET1 in HPV16 E6 induced cervical cancer from tissue, cell and animal three aspects, by using luciferase reporting system, ChIP and CRISPR/CAS9 targeting technology. The results are of great significance for early diagnosis and new treatment of cervical cancer.