Lnc RNA RP11-320N7.1调控cyclin D2对腺性膀胱炎细胞周期的影响及机制研究

Cystitis glandularis is a mucosal proliferative lesion, malignant tendency, in recent years the incidence rate increased gradually. But its specific pathogenesis is still not very clear. Weather we can screen out some specific biomarkers that may indicate the tendency of cystitis glandularis to develop abnormally, and then guide the clinical treatment, which is the key to accurate prevention and treatment of cystitis glandularis. In this study, microarray screening was used in the early stage of the study, and the lncRNAs expression was detected in the tissues of cystitis glandularis and normal bladder mucosa. The expression of lncRNA RP11-320N7.1 was significantly increased in glandular cystitis tissues. According to bioinformatics software analysis: RP11-320N7.1 and cyclin D2 have the same base sequence, and the base were complement to miR-204-5p. Cyclin D2 is an important cell cycle regulatory protein, which can promote cell cycle from G1 phase into the S phase. Therefore, we hypothesized that Lnc RNA RP11-320N7.1 may promote the abnormal proliferation of bladder epithelial cells by acting on the cell cycle critical protein cyclin D2. Using methods such as lncRNA overexpression and knockdown, nude mice xenograft model, we try to comfirm our hypothesis in vitro, in vivo as well as in clinical studies. We aim to further investigate the molecular mechanism at lncRNAs levels in patients with cystitis glandularis.

腺性膀胱炎是粘膜增生性病变，有恶变倾向,发病率递增，但发病机制仍不清楚。筛选出某种提示腺性膀胱炎异常增殖进展倾向的特异性生物标志物，是腺性膀胱炎临床精准防治的关键。我们前期采用基因芯片技术，筛选出在腺性膀胱炎组织中表达显著升高的lncRNA RP11-320N7.1。生物信息学软件分析：RP11-320N7.1和cyclin D2有一段相同的碱基序列，且该序列和miR-204-5p互补。cyclin D2是重要的细胞周期调控蛋白，可促进细胞周期由G1期进入S期。由此推测，Lnc RNA RP11-320N7.1作为ceRNA，通过竞争miR-204-5p调控cyclin D2表达，从而促进膀胱上皮细胞异常增殖。本项目拟通过lncRNA过表达/稳定剔除技术、大鼠动物实验等方法，从体内、体外和临床病理标本等多角度证实这一假设，在“LncRNA层面”进一步研究调控腺性膀胱炎细胞异常增殖的作用机制

腺性膀胱炎是粘膜增生性病变，有恶变倾向,发病率递增，但发病机制仍不清楚。筛选出腺性膀胱炎异常增殖进展倾向的特异性生物标志物，是腺性膀胱炎临床精准防治的关键。我们筛选出在腺性膀胱炎组织中高表达的lncRNA UCA1。通过生物信息学分析推测，Lnc RNA UCA1作为ceRNA，通过竞争miR-204调控cyclin D2表达，从而促进膀胱上皮细胞异常增殖。本项目通过lncRNA过表达/稳定剔除技术、双荧光素酶检测等方法从体内、体外和临床病理标本等多角度证实这一假设，我们证明UCA1通过在腺性膀胱炎原代细胞（pCGs）中吸附miR-204发挥作用，最终揭示了UCA1/miR-204/CCND2调控轴在pCGs中的作用和调控。在“LncRNA层面”进一步研究调控腺性膀胱炎细胞异常增殖的作用机制。