课题组前期研究证实舌鳞癌tumor budding代表恶性程度更高的细胞亚群，细胞内TP63表达上调，与miRNA相互调控，促进肿瘤的生长、转移和干性维持。然而，TP63在非编码RNA调控网络中的作用仍不清楚。进一步研究发现长链非编码RNA TINCR在舌鳞癌tumor budding中显著下调；敲低TINCR可明显促进肿瘤干性维持；生物信息学分析显示TINCR与TP63 mRNA存在结合位点，敲低双链RNA结合蛋白STAU1可增强TP63表达。据此我们推测：TINCR通过招募STAU1诱导TP63 mRNA降解，调控舌鳞癌干性维持。本项目拟在上述工作基础上，分析TINCR与舌鳞癌临床病理及预后相关性；体内外评估TINCR对舌鳞癌干性维持的调控作用；探讨STAU1/TP63信号轴介导TINCR调控舌鳞癌tumor budding细胞干性维持的分子机制，为舌鳞癌的治疗提供新的靶点及实验依据。

Our previous study demonstrated that tumor budding represented the cell subpopulation with more aggressive malignance in tongue squamous cell carcinoma (TSCC). TP63 was upregulated in tumor budding cells, forming the regulatory loop interaction with miRNA, promoted cell growth, metastasis and stem-like phenotype in TSCC. However, the role of TP63 in the non-coding RNA (ncRNA) regulatory network is poorly understood. In further study, we found that long non-coding RNA TINCR was downregulated in tumor budding of TSCC. We also revealed that TINCR deletion significantly promoted cell stemness in TSCC. Then, bioinformatics analysis suggested that TINCR may potentially bind to TP63 mRNA. Moreover, knockdown of double-stranded RNA binding protein STAU1 significantly enhanced the TP63 expression level. Therefore, we hypothesize that TINCR regulates stemness of tumor budding cells through recruiting STAU1 and inducing TP63 mRNA degradation in TSCC. Based on these findings, firstly, we aim to investigate the correlation between TINCR expression and the clinical significance in TSCC patients. Secondly, we will determine the role of TINCR in regulating cell stemness in vitro and in vivo.Thirdly, we further explore the mechanism of TINCR in regulating stemness of tumor budding cells via activation of STAU1/TP63 signaling axis in TSCC. Achievements of this project will provide new strategies for TSCC treatment.