乏氧可诱导食管癌放射抵抗，影响放疗疗效及预后，但乏氧信号途径的调控机制仍不完全清楚。项目组前期对食管癌中异常表达的发育调节转录因子PAX2的功能进行了研究，发现其能影响食管癌细胞的放射敏感性；运用基因芯片技术发现PAX2能调节数百个lncRNA的表达，其中lnc-HIF1A-1受到PAX2激活后能调节乏氧诱导因子HIF-1α的表达及其转录活性。据此我们推测：PAX2可能通过转录调控lnc-HIF1A-1的表达，调节乏氧信号途径，影响食管癌细胞的放射敏感性。本项目拟在前期工作基础上通过多种分子生物学手段探索：1）PAX2转录调控lnc-HIF1A-1的分子机制；2）lnc-HIF1A-1通过调控HIF-1α及乏氧信号途径，对食管癌细胞及移植瘤放射敏感性的影响。本研究有望揭示PAX2/lnc-HIF1A-1通过调控乏氧信号途径对食管癌放射敏感性的影响及机理，为食管癌放射增敏提供新的靶点与策略。

Hypoxia can induce radioresistance, which may affect radiotherapy efficacy and prognosis. However, regulatory mechanisms of hypoxia signaling pathway are not completely clear. Previously, we have reported that PAX2, a key transcriptional factor in development, is overexpressed in esophageal cancer tissues and plays a critical role in the progression of esophageal cancer. And PAX2 affected the radiosensitivity of esophageal cancer cells. By lncRNA microarray, we found that PAX2 could activate multiple lncRNAs, including lnc-HIF1A-1. And Inhibition of lnc-HIF1A-1 downregulated the expression of HIF-1α expression in esophageal epithelial cells. Therefore, we postulate that PAX2 is likely to modulate hypoxia signaling pathway and radiosensitivity by activating lnc-HIF1A-1 in esophageal epithelial cells. This project will utilize multiple molecular biological techniques at the cellular level and animal level to investigate: 1) The mechanism of PAX2 in transcriptional regulation of lnc-HIF1A-1 expression; 2) The effect of lnc-HIF1A-1 on the radiosensitivity of esophageal cancer cells and xenografts by modulating HIF-1α expression and hypoxia signaling pathway. This project will contribute to our understanding of PAX2/lnc-HIF1A-1 pathway in modulating the radiosensitivity of esophageal cancer cells, which can provide novel targets and therapeutic strategies in esophageal cancer radiosensitization.