p53突变获能是口腔鳞癌恶性进展的重要驱动因子，但长链非编码RNA是否参与突变获能及其机制迄今不明。我们前期研究发现：p53-R282W抑制lincRNA-p21的转录活性，同时上调细胞分裂周期蛋白7（Cdc7）表达，促进G1/S期转化；lincRNA-p21与核内不均一核糖核蛋白K存在直接结合。据此提出假说：lincRNA-p21募集核内不均一核糖核蛋白K沉默Cdc7的表达，p53-R282W转录抑制lincRNA-p21进而激活Cdc7，导致细胞周期检查点失控。本课题拟运用流式细胞术、ChIP和双荧光素酶报告等技术，揭示长链非编码RNA和p53突变获能之间的直接联系；阐明lincRNA-p21核糖核蛋白复合体在p53-R282W调控Cdc7中的作用机制；明确p53-R282W/lincRNA-p21/Cdc7通路在口腔鳞癌周期调控及恶性进展中的关键作用，为探索新的治疗靶点提供实验依据。

The p53 gain-of-function mutations play critical roles in the progression of oral squamous cell carcinoma (OSCC). However, whether long non-coding RNAs (lncRNAs) participate in the p53-R282W gain of function is unknown. Our recent findings observed that overexpression of mutant p53-R282W promoted the expression of cell division cycle 7 (Cdc7) and G1/S phase transition, but inhibited the transcriptional activity of long intergenic noncoding RNA p21 (lincRNA-p21) promoter in OSCC. In addition, lincRNA-p21 directly bound to heterogeneous nuclear ribonucleoprotein K (hnRNP K). According to the previous results and literature reports, we hypothesize that lincRNA-p21 could recruit hnRNP K as a molecular scaffold, then silence the Cdc7 expression in OSCC. P53-R282W mutation transcriptionally inhibits lincRNA-p21 expression, which results in overexpression of Cdc7 to promote G1/S checkpoint out of control. Flow cytometry, Chromatin immunoprecipitation (ChIP) and dual-luciferase report gene system will be used to elucidate the relationship between lncRNAs and mutant p53, and to clarify the mechanism of lincRNA-p21 ribonucleoprotein complex in the regulation of Cdc7 by p53-R282W. We will also clarify the crucial role of p53-R282W/lincRNA-p21/Cdc7 pathway in OSCC cell cycle regulation and malignant progression. Our study can provide theoretical basis for exploring new therapeutic targets for OSCC.