含WW结构域的氧化还原酶（WWOX）通过抑制AP-1转录活性抑制HPV E6/7导致的宫颈癌进展

经典理论认为高危型HPV感染导致宫颈癌发生，然而HPV感染后宫颈癌发生比率仅为1%，其余病例趋向消散或停滞于CIN1、CIN2，预后差异原因目前尚不清楚。WWOX在宫颈癌中表达缺失，抑制宫颈癌增殖、促进凋亡，其机制尚不明确。两者之间是否存在调控关系也未见报道。本研究试图阐明WWOX与HPV E6/7之间的关系。课题组预实验表明：过表达WWOX下调HPV E6/E7的转录及翻译；减少宫颈癌细胞增殖活性；抑制转录因子AP-1表达；激光共聚焦实验证实WWOX与AP-1共定位；过表达WWOX使AP-1向细胞质方向转位。本课题拟在预实验基础上验证WWOX对HPV E6/E7的调控作用；检测该调控对宫颈癌生物学行为的影响；探讨WWOX对HPV E6/E7的调控机制；并探索使用小分子药物治疗宫颈癌的可行性。研究将在理论上深化对HPV感染致宫颈癌的理解，为个体化分子靶向治疗提供有价值的实验依据。

The classic theory indicates that high risk HPV (human papilloma virus) infection would induce cervical cancer. However,the incidence is very low (about 1%). The most cases recover back to normal or stay in the CIN1/2. The reason why the difference exists remains unclear. WWOX (WW domain-containing oxidoreductase) is down regulated in cervical cancer. Whether there is some relationship between HPV and WWOX needs to be explored. In the former study, we already find out that WWOX can reduce the HPV E6/7 transcription and translation; WWOX can reduce the expression of transcription factor AP-1; WWOX can induce AP-1 translocation from nuclear to cytoplasm. The study will deepen the complex understanding of WWOX and HPV E6/7, and provide a valuable experimental basis for individualized molecular targeted therapy.