人宫颈癌细胞染色体box C/D snoRNA的功能研究

The relationship between noncoding RNA and disease is the focus of current research. Noncoding RNA has a significant subcellular localization, so the enrichment of specific molecular species in cell structure can provide the basis for the related mechanism research. Mitotic chromosome is one of the most important subcellular structures, so its RNA composition will carry important information of cell fate determination. Our previous study showed that mitotic chromosomal RNA contained large amount of box C/D snoRNA. As the most aboundant mitotic chromosomal snoRNA, U3 and U8 were confirmed to relate to tumorigenesis. Cervical cancer remains one of the leading causes of cancer-related deaths worldwide, there are about 500 thousand new cases arose and 240 thousand patients died each year. There are about 100 thousand new cases each year in China. In this project, we will study the characters and differences of mitotic metaphase chromosome RNA and interphase chromatin RNA from human cervical cancer cell and normal human cervical epithelial cell by using the mitotic chromosome isolation technique also with molecular biology methods, immune fluorescence in situ hybridization and RNA interference technique. Study on the mechanism of cell cycle dependent mitotic chromosomal box C/D snoRNA with cervical cancer in the cell, clinical samples and model animal will reveal new potential therapeutic targets for cervical cancers.

非编码RNA与疾病的相关性是目前的研究热点。非编码RNA具有显著的亚细胞定位特点，因此细胞结构中特定分子种类的富集可以为相关的机制研究提供依据。有丝分裂染色体作为最重要的公认亚细胞结构之一，其RNA组成一定会携带重要的细胞命运决定信息。我们前期的实验发现有丝分裂中期染色体有大量的box C/D snoRNA，同时已经被证实与癌症的发生有关的U3和U8，是其中丰度最高的两种snoRNA。宫颈癌是常见的妇科恶性肿瘤，据统计，世界范围每年约有53万新发病例及27万患者死亡。本项目通过人宫颈癌细胞和正常宫颈上皮细胞有丝分裂中期染色体及间期染色质RNA的特征性组成及差异性分布为切入点，在细胞，临床样本和动物模型三个水平，采用特殊亚细胞结构的分离提取及分子生物学、免疫荧光原位杂交技术和RNA干扰等技术，研究细胞周期性变化的染色体box C/D snoRNA与宫颈癌发病的相关性，揭示新的宫颈癌治疗靶点。