16型人乳头瘤状病毒（HPV16）早期基因E6/E7剪接调控与肿瘤发生的分子机制

高危型人乳头瘤状病毒（human papillomavirus）感染与包括女性宫颈癌在内的生殖器官癌症以及包括口咽癌在内的头颈癌高度相关。虽然研究发现HPV的致癌性与早期蛋白E6、E7的表达直接相关，但是就E6/E7前体RNA是如何通过剪接调控E6^E7 mRNA和E6* I^E7 mRNA的协同表达从而使感染细胞转化癌变还未见报道。SR和hnRNP家族蛋白是核内RNA结合蛋白，能够调节RNA生命周期的大部分过程，对前体RNA的剪接非常重要，研究发现这两类蛋白在肿瘤细胞中均高表达。本项目拟通过研究SR和hnRNP家族蛋白对E6/E7前体RNA剪接调控的分子机制，结合分析临床样本中E6^E7 mRNA和E6* I^E7 mRNA的比例关系，来探索HPV感染致癌的深层分子机制。本研究的开展对于阐释HPV致癌分子机制以及针对这一机制进行药物开发，从而有效地控制HPV感染诱发的癌症具有重要意义。

High-risk Human Papillomavirus is present in cervical cancer and is tightly associated with other anogenital cancers as well as head and neck cancers. Around 530,000 cases of cervical cancer are diagnosed each year in the world and head and neck cancers are now ranked at the top 6 cancer. HPV’s transforming potential is directly related with HPV early genes E6 and E7, which is encoded by polycistronic preRNA. However, no research data on how the alternative splicing is associated with HPV‘s transforming ability is presented yet. SR and hnRNP proteins are RNA binding proteins and are highly expressed in tumor cells. SR and hnRNP proteins are involved in preRNA splcing process. This project is aimed to explore the initial mechanism of E6/E7 preRNA splicing regulation by SR and hnRNP proteins, and discover how the ratio of E6^E7 mRNA and E6* I^E7 mRNA is balanced during the regulation. This study is helpful to understand HPV’s transforming mechanism, design specific anti-tumor drugs and control cancer induced by HPV infection.