肠炎-癌转化中小RNA体内靶基因的鉴定和预测算法的研究

小RNA可调控包括炎症、癌症等许多生理进程中的重要基因表达。虽然已有多种小RNA靶基因预测算法，但对寻找小RNA体内靶基因的帮助还很有限。本课题针对上轮课题研究中所遇到的问题无法准确全面地鉴定小RNA在炎症肠上皮中的靶基因，计划基于近期通过结合基因组学、定量蛋白质组学和多核糖体展示等多种方法所鉴定到的miR-17～92族小RNA在原代B细胞中的真实靶向基因的数据，发展一种新的小RNA靶基因预测算法；以肠炎相关的肠癌为模型，运用上述可行的多种技术的结合，鉴定miR-17～92家族小RNA在炎症肠上皮细胞中的靶基因，研究其对炎-癌转化的影响；肠上皮实验所得到的数据还将用来验证和优化我们开发出来的小RNA靶基因预测算法；然后运用此算法于miR-21在肠炎-癌转化中作用的研究中。我们的工作将会促进人们对于小RNA在肠炎诱发的肠癌中作用的理解，同时提供一个有效的小RNA体内靶基因的预测算法。

MicroRNAs (miRNAs) regulate gene expressions in a variety of cellular processes such as inflammation and cancer. Although a number of miRNA target prediction algorithms are available, their role in finding miRNA’s in vivo target genes is very limited. This proposal focuses on the problem arising in the previous funding period of our study that we were unable to identify precisely and comprehensively the miRNA’s in vivo target genes in intestine epithelial cells (IECs). To solve this problem, we have identified miR-17～92 family miRNAs’ target genes in an easily obtained primary B cell by combination of several approaches including genomics, quantitative proteomics, and polysome profiling, and will utilize these data to develop a miRNA targets prediction algorithm. We will re-apply above mentioned combination approach to IECs and identify the in vivo target genes of miR-17～92 family miRNAs and study their role in tumorigensis of colitis-related colon cancer. The data obtained from IECs will be used to test and optimize our prediction algorithm, which would be applied to investigate the role of miR-21 in inflammation-induced colon cancer. This work will lead to a better understanding of the function of miRNA in colitis-related colon cancer and provide an effective experimental data-based miRNA in vivo targets prediction algorithm.