长非编码RNA CILA调控舌鳞癌化疗耐受的研究

Cisplatin-resistance is the main inhibitor of chemotherapy efficacy for tongue squamous cell carcinoma (TSCC). To improve chemotherapy efficacy, we should investigate the mechanisms that regulate cisplatin-sensitivity, and look for the methods to reverse cisplatin-resistance and the methods for targeted therapy. Our group has studied the mechanism of microRNA in regulating chemotherapy-induced EMT (Epithelial-Mesenchymal Transtion) of tongue cancer cells. To investigate the mechanism of long noncoding RNA (lncRNA) in regulating chemotherapy-resistance of TSCCs comprehensively, we intend to screen lncRNAs. We will compare expressions of lncRNA in TSCCs cells before and after cisplatin treatment, and select 2-3 lncRNA CILA (Chemotherapy-Induced Long noncoding RNA) that are upregulated significantly in chemotherpy- resistant TSCC cells. Then we would intervene expression of CILA and investigate regulation of CILA on chemotherapy sensitivity in vitro and in vivo. And detecting association of CILA expreesion and chemotherapy sensitivity of TSCC samples, or outcome of TSCC patients. At last, we will detemine the protein that interacting with CILA and elaborate the molecular mechanism of CILA in regulating chemotherapy-resistance.

顺铂耐药是影响舌鳞癌化疗疗效的主要因素，探讨影响顺铂敏感性的相关因素，研究逆转耐药和靶向治疗的方法，对提高舌鳞癌化疗疗效具有重要意义。 本课题组已经具有microRNA调控舌鳞癌细胞化疗诱导EMT的研究基础，为更全面地探讨长非编码RNA对舌鳞癌化疗耐受的调控机制，本项目拟从长非编码RNA的功能筛选进行研究。我们将比较顺铂处理前后舌鳞癌细胞中长非编码RNA的表达差异，筛选2-3个显著上调的lncRNA CILA（Chemotherapy-Induced Long noncoding RNA），干预舌鳞癌细胞CILA的水平，在细胞和动物模型中观察CILA对化疗敏感性的调控作用，同时在临床样本中检测CILA表达水平与舌鳞癌化疗敏感性、患者预后的关系，并确定与CILA相互作用的蛋白，阐明CILA调控舌鳞癌化疗耐受的分子机制。

顺铂耐药是影响舌鳞癌化疗疗效的主要因素，探讨影响顺铂敏感性的相关因素，.研究逆转耐药和靶向治疗的方法，对提高舌鳞癌化疗疗效具有重要意义。 本课题组已经具有microRNA调控舌鳞癌细胞化疗诱导EMT的研究基础，为更全面地探讨长非编码RNA对舌鳞癌化疗耐受的调控机制，本项目拟从长非编码RNA的功能筛选进行研究。我们比较顺铂处理前后舌鳞癌细胞中长非编码 RNA 的表达差异，筛选在化疗耐药细胞中显著上调的 lncRNA CILA（Chemotherapy-Induced Long noncoding RNA），通过升高亲本细胞中lncRNA CILA1后与亲本细胞比较发现多个差异表达的基因，这些变化明显的基因涉及wnt/beta-catenin 信号通路，进一步研究发现，在化疗耐药细胞中降低lncRNA CILA1表达水平后，可促进beta-catenin 磷酸化，进而抑制beta-catenin入核，从而抑制wnt/beta-catenin 信号通路的激活。在临床样本中检测lncRNA CILA1异常表达与患者预后以及转移的关系,发现高表达lncRNA CILA1预后较差,转移率高。