外泌体lncRNA NR_015395通过SMAD3调控EMT影响腺性膀胱炎复发、进展的作用机制研究

腺性膀胱炎（GC）为储尿期排尿异常的主要疾病，严重影响患者生活质量。而目前其发病机制不清、药物疗效不佳、术后易复发，分子机制研究亟缺。申请人前期通过基因芯片发现了GC与正常膀胱粘膜组织中大量差异表达的lncRNAs、mRNAs，其中lncRNA NR_015395、SMAD3在GC组织中表达均显著增加，临床小样本也验证了lncRNA NR_015395在GC组织和外泌体中高表达。生物信息学分析预测NR_015395可能与SMAD3共同竞争结合miR-133a-3p。据此申请人提出假设：GC细胞分泌的外泌体lncRNA NR_015395通过SMAD3影响上皮间质转化（EMT）过程，从而调控GC疾病复发、演进。本课题拟通过高通量芯片、细胞学、动物模型、临床研究等方法，从体外、体内和临床等多维度来验证，以阐明上述信号调控通路为核心的腺性膀胱炎复发、进展机制，为其精准诊治、预防复发提供新策略。

Glandular cystitis (GC) is a disease of abnormal urination during relaxation phases, which seriously affects patients’ life quality. Its pathogenesis remains unclear, therapeutic effects are not satisfactory, post-surgery recurrence rate is high. However, its systematic molecular studies are lacking. Through microarray screening, we found large amount of dysregulated lncRNAs and mRNAs in GC vs. normal bladder tissues. And the expression of lncRNA NR_015395 and SMAD3 were elevated in GC tissues and this result was also confirmed by small sample analysis. Bioinformatics analysis predicted lncRNA NR_015395 might compete with SMAD3 on binding to miR-133a-3p through ceRNA mechanism. Based on above, we hypothesize that exsosome lncRNA NR_015395 may impact SMAD3 signaling to influence epithelial-mesenchymal transition (EMT), thus promotes the recurrence and progression of GC. This project intends to verify this hypothesis by in vitro, in vivo and clinical studies through microarray, cell line, animal model and clinical sample analysis, etc. We aim to elucidate the mechanism of GC with the exsosome lncRNA NR_015395/ SMAD3 signaling and provide new therapeutic targets and novel strategies for its precise diagnosis, treatment and recurrence preventing.