微小RNA作为膀胱尿路上皮癌早期诊断标记物的研究及其在发病机制中的功能分析

MicroRNAs (miRNAs) are a class of eukaryotic endogenous small non-coding RNA molecules with lengths about 22 nucleotides, mainly function at post-transcriptional level to regulate gene expression by pairing with mRNAs via nucleotide complementarity. Many lines of evidence have shown that miRNAs may act as either oncogenes or tumor suppressors and involve in the development of multiple cancers. In recent years, researches have found that circulating cancer-related miRNAs can be detected in human plasma,serum or urine samples, and their expression levels are correlated with the types and degrees of cancers. Thus miRNAs are very promising to serve as biomarkers for the early diagnosis and classification of cancers. Bladder urothelial carcinoma is one of the most commonly seen urinary system cancer, with significantly increased occurance rate in China in recent years. cystoscopy is the main diagnostic and follow up method for bladder cancer, but it causes severe patient's pain. Therefore, to identify a more sensitive and more specific diagnostic method with minimal pain is of great needs and application values. This project plans to systematicly examine the expression profiles of small RNAs within the tissue, blood and urine samples of patients and controls, to identify miRNAs with expression changes and qualified to serve as biomarkers for the early diagnosis and classification of bladder urothelial carcinoma, to perform target identification as well as functional studies of selected miRNAs for their roles in causing the disease.

微小RNA(miRNA)是真核细胞内一类约22个核苷酸长的非编码小分子RNA，主要通过碱基互补与mRNA结合参与转录后的基因表达调控。大量研究表明miRNA既可作为癌基因，又可作为抑癌基因，在多种肿瘤的发生与发展过程中起重要作用。近年来发现一些在肿瘤与正常组织之间差异表达的miRNA可以在血清中被检测到，具有与肿瘤组织中类似的表达谱，并且在不同恶性程度的肿瘤患者间存在表达差异，因此有可能作为肿瘤早期诊断与分型的分子标记物。膀胱尿路上皮癌是泌尿系统最常见的恶性肿瘤之一，近年来在我国的发病率显著增长。膀胱镜是临床诊断和术后随访膀胱肿瘤的主要方法，但存在病人痛苦大等问题。因此，寻找一种高灵敏性与特异性且创伤小的诊断方法极具临床价值。本项目拟对膀胱尿路上皮癌患者的疾病组织、血浆和尿液中表达的小分子RNA进行系统筛查，发现可能用于疾病早期诊断与分型的miRNA，并对其中部分miRNA的功能进行研究。

微小RNA(miRNA)是真核细胞内一类约22个核苷酸长的非编码小分子RNA，主要通过碱基互补与mRNA结合参与转录后的基因表达调控。大量研究表明miRNA既可作为癌基因，又可作为抑癌基因，在多种肿瘤的发生与发展过程中起重要作用。膀胱尿路上皮癌是泌尿系统最常见的恶性肿瘤之一，近年来在我国的发病率显著增长。膀胱镜是临床诊断和术后随访膀胱肿瘤的主要方法，但存在病人痛苦大等问题。因此，寻找一种高灵敏性与特异性且创伤小的诊断方法极具临床价值。我们对膀胱尿路上皮癌患者血液中表达的小分子RNA进行系统筛查，得到了一些显著差异表达的miRNA，它们可能作为疾病早期诊断与分型的分子标记物。同时，我们还鉴定得到一个在肿瘤患者中高表达的新miRNA，该miRNA能特异靶向调控膀胱肿瘤途径中的关键基因。