hTERT高表达是肿瘤进展的重要指标，深入研究其调控机制非常必要。预实验我们采用DNA结合蛋白垂钓系统和质谱技术，在食管癌细胞中鉴定出新的hTERT启动子结合蛋白RFX1和CREBBP，并发现它们可相互作用，影响hTERT启动子活性和细胞增殖。但它们调控hTERT表达和功能及在食管癌中的临床意义均不明确。为此，我们将在食管癌细胞及动物模型中，过表达或敲除RFX1和CREBBP，研究它们的生物学功能及相互结合位点，以及它们对hTERT基因表达、端粒酶活性、端粒长度，细胞增殖、肿瘤形成及相关信号通路的影响，明确其调控食管癌生长的分子机制。另外，用组织芯片检测RFX1、CREBBP和hTERT的表达，结合临床资料分析其与TNM分期、转移、复发和生存等相关性，明确其临床意义。本项目将揭示hTERT调控新机制和食管癌发病机理，为确立RFX1/CREBBP/hTERT作为食管癌治疗新靶点提供实验依据。

High expression of hTERT is an important indicator of tumor progression, so it is necessary to further study its regulatory mechanism. In the preliminary experiment, we identified the new hTERT promoter binding proteins RFX1 and CREBBP in esophageal cancer cells using DNA-binding protein pulldown system and mass spectrometry, and found that they could interact with each other and affect hTERT promoter activity and cell proliferation. However, it remain unclear about the regulation of RFX1 and CREBBP on hTERT expression and their function and clinical significance in esophageal cancer. In this study, we will knock down or overexpress RFX1 and CREBBP in esophageal cancer cells and animal models and study their biological functions and interacting sites, as well as effects on hTERT gene expression, telomerase activity, telomere length, cell proliferation, tumor formation and the related signal pathways, thereby identifying the molecular mechanism of RFX1 and CREBBP in regulating esophageal cancer growth. In addition, we will detect the expression of RFX1, CREBBP and hTERT in tumor tissues using tissue microarray, and analyze their correlation with TNM staging, metastasis, recurrence and survival in combination with clinical data, so as to clarify its clinical significance.This project will reveal the new mechanism of hTERT regulation and the pathogenesis of esophageal cancer, and provide experimental basis for establishing RFX1/CREBBP/hTERT as a new therapeutic target for esophageal cancer.