长非编码RNA调控化疗诱导的舌鳞癌细胞EMT的机制研究

非编码RNA对肿瘤细胞生物学特性的调控作用日益受到重视，本课题组既往研究了miRNA对舌鳞癌增殖凋亡、侵袭转移的调控作用，最近又研究发现顺铂化疗耐受的舌鳞癌细胞发生了上皮-间质转化（EMT），并在顺铂耐药的舌鳞癌细胞中筛选到一组差异表达的长非编码RNA（lncRNA）。为进一步探讨非编码RNA对舌鳞癌生物学特性的调控机制，本项目从lncRNA角度，研究其对化疗压力下舌鳞癌细胞产生的EMT的调控作用。将从预实验中获得的耐药细胞lncRNA表达谱中挑选数个差异显著的lncRNA，通过干预舌鳞癌细胞lncRNA水平，在细胞和动物模型中观察lncRNA对化疗诱导EMT、化疗敏感性的调控作用及侵袭迁移能力的影响，并确定与lncRNA相互作用的蛋白，检测其表观遗传学改变，同时在临床样本中检测lncRNA异常表达与化疗敏感性、患者预后的关系，阐明lncRNA调控化疗压力下舌鳞癌细胞可塑性的生物学机制。

Tumor cellular plasticity, which mainly recognized as epithelial-mesenchymal transition (EMT), is the essential cause of tumor heterogeneity and chemotherapy resistance. Recently the role of non-coding RNA, including microRNA (miRNA) and long non-coding RNA (lncRNA) in regulating biological characteristics of tumor cells has received more and more attention. Our group has studied roles of miRNA in regulating proliferation, apoptosis, metastasis and chemoresistance of tongue squamous cell carcinoma (TSCC). In order to study the role of non-coding RNA more comprehensively, we intend to investigate roles of lncRNAs in regulating TSCC cellular plasticity. We will select lncRNAs that are differentially expressed in chemotherapy-resistant TSCC cells and parental TSCC cells, interfere their expression and investigate their functions in regulating chemotherapy induced EMT, chemotherapy sensitivity, and invasiveness by using cellular and animal models. Then we will correlate expression of functional lncRNAs with chemotherapy sensitivity and prognosis of TSCC patients and identify the lncRNA interacting proteins to discover the molecular mechanisms of lncRNA in regulating cellular plasticity of TSCC cells under chemotherapy pressure.