细胞周期失调控影响肿瘤细胞增殖。我们首次发现miR-424-5p在食管鳞癌中高表达，且具有促癌作用。预实验表明：食管鳞癌中，miR-424-5p表达随细胞周期进程改变；通过调控靶基因Npm1及Wee1表达，促进细胞跨越细胞周期检测点，加速细胞增殖。然而，食管鳞癌中miR-424-5p高表达，且表达随细胞周期进程变化原因未明，推测与转录调控及转录后修饰相关；其对靶基因的调控存在细胞异质性，推测有其他非编码RNA作为ceRNA影响其功能。为了验证这一以miR-424-5p为核心，由转录因子、靶基因和ceRNA等构成的细胞周期调控网络，我们将从动物-细胞-分子三个层次，体内外观察miR-424-5p表达对食管鳞癌增殖的影响；阐明其在食管鳞癌中高表达的原因；明确miR-424-5p及ceRNA对靶基因表达和细胞周期进程的调控。本课题将揭示细胞周期调控的新机制，为寻找食管鳞癌预后分子标志物奠定基础。

Deregulation of cell cycle plays an important role in tumor cell proliferation. We found that miR-424-5p was overexpressed and might function as an oncogene in esophageal squamous cell carcinomas (ESCCs), but the specific mechanism has not been determined. Preliminary experiments showed that expression of miR-424-5p was up-regulated in ESCCs and varied along with cell cycle progression, which further down-regulated the expression of targeted genes Npm1 and Wee1 and promoted cell cycle progression and cell proliferation. However, the reason why miR-424-5p was up-regulated in specific cell cycle of ESCC cells has not been determined, which might be due to transcriptional regulation and post-transcriptional modification of miR-424-5p per se. And miR-424-5p exhibited heterogeneity in regulating target genes’ expression, probably because of the effect of other non-coding RNAs as competing endogenous RNAs (ceRNAs). In order to reveal the cell cycle regulation network composed of transcription factor, miR-424-5p, target coding genes, and non-coding RNAs functioning as ceRNAs in this study, we plan to observe the effect of miR-424-5p in ESCC proliferation in vitro and in vivo, identify factors inducing high miR-424-5p expression in ESCCs, and illuminate the specific role of miR-424-5p and ceRNA in regulating target genes’ expression and cell cycle progression. The study would provide an alternative mechanism to understand the ESCC cell cycle regulation, and lay foundation for the identification of useful ESCC prognostic molecular markers.