一个新的p53下游长链非编码RNA抑制胃癌进展的作用及机制研究

长链非编码RNA（long noncoding RNA, lncRNA）与肿瘤关系密切，是新的研究热点。我们前期在胃癌中筛选了一个具有抑癌作用的lncRNA-RP11-223J15.2，初步证实其能调控胃癌的细胞周期和细胞凋亡。通过生物信息学分析和预实验，我们提出p53转录调控该lncRNA表达的可能性，但具体机制和发挥作用的模式未明。基于此，本项目拟首先在组织和细胞水平上获得RP11-223J15.2抑制胃癌作用的可靠证据；然后采用基因转染、报告基因和CHIP等方法，证实p53对其转录调控的作用；最后通过寻找RP11-223J15.2的下游效应分子，鉴定其RNA结合蛋白和寻找以竞争性内源性RNA 模式作用的miRNA，完善该lncRNA的调控网络，并与临床相结合，阐述其生物学意义。本项目有望揭示一个新的p53下游的lncRNA发挥抑癌作用的分子机制，从而为胃癌的治疗提供新的思路和靶点。

Long noncoding RNA (lncRNA) is closely associated with cancer, which becomes a new research focus. Our previous research found a new lncRNA-RP11-223J15.2 in gastric cancer with a potential role of tumor suppression. Preliminary results confirmed that RP11-223J15.2 could regulate cell cycle and apoptosis in gastric cancer. By bioinformatics analysis and preliminary experiments, we propose that p53 can regulate the expression of RP11-223J15.2 at transcriptional level, while the mechanism remains to be elucidated. This project will firstly confirm that RP11-223J15.2 plays an anticancer role in gastric cancer. Furthermore, we will prove that p53 can regulate the expression of RP11-223J15.2 through the transcriptional level. Finally, we will seek downstream molecules for RP11-223J15.2, identify the lncRNA binding protein and find the miRNAs with competing endogenous RNA model, thus perfect the regulation network of this lncRNA and explain its biological significance combined with clinical data. This project aims to illuminate the mechanism of a new identified downstream lncRNA of p53 to suppress the progression of gastric carcer, which is supposed to provide a new target for the treatment of gastric cancer.