HPV16 E7/ASF1B/RacGAP1调控细胞胞质分裂对病毒持续感染及宫颈癌发生的影响

宫颈癌仍是严重威胁女性健康的恶性肿瘤。高危人乳头瘤病毒（hrHPV）持续感染是宫颈癌发生的必要因素，其致癌过程中仍有许多关键环节尚未阐明。胞质分裂（cytokineses）与多种致瘤病毒引起的病毒持续感染导致肿瘤的发生密切相关，但在宫颈癌中尚无研究报道。我们对宫颈组织及细胞的转录组测序进行分析发现HPV16 E7（16E7）可以通过调控ASF1B上调RacGAP1帮助病毒在细胞中持续存在，促进细胞胞质分裂，导致宫颈高级别病变甚至癌的发生。本项目从宫颈组织和细胞的转录组测序分析出发，经组织标本验证、基因调控技术、活细胞成像、裸鼠成瘤等探索16E7调控胞质分裂的具体机制，最后通过组织标本体内验证各个分子间的表达和相关性，统计并分析与临床数据的关系，完整阐述16E7/ASF1B/RacGAP1调控细胞胞质分裂对病毒持续感染及宫颈癌发生的影响，为临床治疗或逆转宫颈癌提供科学依据。

Cervical cancer is a big threat to women all over the world. Persist infection of high-risk pipallomavirus (hrHPV) is essential to cervical carcinogenesis. E7 is supposed to be the most important virus oncoprotein. Cytokinesis has been found to be involved in kinds of tumor but there is no study on cytokinesis in cervical cancer. In our research, transcriptome sequencing for cervical tissue and cell has been analysis and RacGAP1, with is regulated by 16E7 and to be associated with cytokinesis, is selected for further study. ASF1B is found to be the molecular in 16E7 modulating RacGAP1. Clinical samples are utilized to detect the expression of 16E7，ASF1B and RacGAP1. In our study, a new pathway of HPV16 E7/ASF1B/RacGAP1 on promoting cytokinesis is clarified. We hope our study will provide new thoughts in prophylaxis and treatmeat to HPV associated tumors.