CCAT1在宫颈癌发病中作用机制研究及其靶向逆转

本项目前期工作通过高通量测序检测宫颈癌发现长链非编码RNA CCAT1是HPV的高频整合位点。进一步发现CCAT1在临床宫颈癌组织样本中的表达明显上调，并促进形成宫颈癌细胞增殖恶性表型。本项目拟在此基础上，一方面从机制研究角度出发，利用RNA免疫共沉淀实验、pull down、RNA sequencing、荧光素酶报告系统等技术，充分阐明CCAT1通过调控miR-181a-5p/MMP14通路和直接作用基因促进宫颈癌细胞增殖的机制；另一方面，从应用角度出发，构建靶向CCAT1的PBAE纳米颗粒，分析其理化性状特征，从细胞、临床标本、载瘤小鼠、HPV转基因小鼠等多角度评估靶向CCAT1的PBAE纳米颗粒的生物安全性和治疗CIN和宫颈癌的疗效。本项目将阐明CCAT1在宫颈癌发病中的作用机制，探并索宫颈靶向治疗的新策略。

Our previous work showed that long non coding RNA CCAT1 was a high frequency integration site for HPV in cervical cancer by high-throughput sequencing. It was further found that the expression of CCAT1 was up-regulated in clinical cervical cancer tissue samples and promoted the proliferation of cervical cancer cells. Based on previous findings, this project is planned to fully elucidate the mechanism by which CCAT1 promotes proliferation of cervical cancer cells by regulating miR-181a-5p/MMP14 pathway and direct acting genes. On the other hand, this project is to construct CCAT1 targeted PBAE nanoparticles, analyze its physical and chemical properties, evaluate the biosafety and treatment effect in CIN and cervical cancer in cells, clinical specimens, tumor-bearing mice, HPV transgenic mice, etc. This project will clarify the mechanism of CCAT1 in the pathogenesis of cervical cancer, and explore a new strategy for targeted therapy in uterine cervix.