食管癌恶性程度高治疗效果差，肿瘤干细胞在食管癌的发生发展及治疗过程中具有重要意义。谱系追肿瘤干细胞在生物体内的起源和发生发展过程是当今国际研究热点，但目前尚缺乏特异的食管肿瘤干细胞谱系追踪标记物。miR-203和Bmi-1是我室前期发现的食管肿瘤干细胞关键调控分子。Bmi-1是miR-203的靶基因，miR-203通过调控Bmi-1来调控食管肿瘤干细胞的自我更新。研究提示miR-203和Bmi-1可作为潜在的谱系追踪标志物进行研究。本研究将在大鼠食管上皮中验证miR-203和Bmi-1能否作为正常食管干细胞的分子标记。在人食管癌细胞系和原代培养的食管癌细胞中验证其能否作为食管肿瘤干细胞的标志物。最终在亚硝胺诱导大鼠成食管癌的模型中，验证miR-203和Bmi-1能否作为用于谱系追踪的食管肿瘤干细胞的标志物。本项目可为揭示食管肿瘤干细胞在生物体内起源和作用机制研究奠定基础，有利于肿瘤的防治。

Esophageal cancer has high malignancy rate and the prognosis of esophageal cancer treatment is poor till now. Cancer stem-like cells have been indicated to play critical roles in the occurrence, development and treatment of esophageal cancer. Using the lineage tracing method to trace the occurrence and development of cancer stem-like cells is a hot field of the current international cancer research. However, there is so far no report on specific lineage tracing markers for the esophageal cancer stem-like cells. In our previous study, we have identified that miR-203 and Bmi-1 play critical roles in the maintenance of esophageal cancer stem-like cells. We have found that Bmi-1 is a direct target of miR-203 and miR-203 regulates esophageal cancer stem-like cells by suppressing Bmi-1 expression. Our results indicated that miR-203 and Bmi-1 could be potential lineage tracing markers for esophageal cancer stem-like cells. In this proposal, we are going to investigate whether miR-203 and Bmi-1 could be specific markers for normal stem cells of esophagus of rats. Then, we will identify if miR-203 and Bmi-1 are specific markers for cancer stem-like cells isolated from both the human primary esophageal cancer tissue and the human esophageal cancer cell lines. Finally, we are going to identify if miR-203 and Bmi-1 could be lineage tracing markers for esophageal cancer stem-like cells in the rat induced esophageal cancer model. This study will contribute to reveal the mechanism of the occurrence and development of esophageal cancer stem-like cells, and help to develop potential therapeutic strategies of esophageal cancer.