HuR调控Snail影响EMT在食管癌放射敏感性中的作用及机制研究

Radiotherapy is one of the main treatments for esophageal cancer. The radiation field tumor recurrence and distant metastasis are the main reasons for treatment failure. Epithelial mesenchymal transition (EMT) increases the resistance of tumor cells to radiation therapy and is closely associated with tumor recurrence after radiotherapy. Snail is a key transcription factor of EMT and is involved in tumor resistance. HuR is one of mRNA binding proteins, which is widely involved in post-transcriptional regulation of genes and highly expressed in a variety of tumors. Our group has reported that HuR highly expressed in esophageal cancer tissues and affected the expression of EMT related proteins. Previous studies have also shown that HuR regulated the expression of Snail protein as well as the apoptosis and the cloning efficiency of esophageal cancer cells induced by radiation. Based on the above research, this project is to further reveal: 1) The molecular mechanism of the occurrence of EMT affected by Snail post-transcriptional regulated by HuR in esophageal cancer.2) The effect of HuR on the radiosensitivity of esophageal cancer by regulating EMT via Snail at the cellular level and animal level.This project is expected to reveal a new mechanism of HuR/Snail pathway to regulate the radiosensitivity of esophageal cancer and provide new targets and strategies for radiotherapy of esophageal cancer.

放射治疗是食管癌的主要治疗手段之一，放射野内肿瘤复发及远处转移是治疗失败主要原因。上皮间质转化（EMT）增加了肿瘤细胞对放射治疗的抗性并与放疗后肿瘤复发密切相关。Snail是EMT的关键转录因子并参与肿瘤的放射抵抗。HuR是一种mRNA 结合蛋白，广泛参与基因的转录后调节，并在多种肿瘤中高表达，但是否参与食管癌放射敏感性调节尚不清楚。本项目组前期报道了HuR在食管癌组织中高表达，并影响EMT相关蛋白表达。前期研究还发现HuR可调节Snail蛋白的表达并影响放射引起的食管癌细胞的凋亡和克隆形成。本项目拟在上述研究基础上进一步揭示：1）HuR通过转录后调控Snail影响食管癌EMT过程的分子机理；2）在细胞水平和动物水平阐明HuR通过Snail调节EMT对食管癌放射敏感性的影响。本项目有望揭示HuR/Snail通路调控食管癌放射敏感性的新机制，为食管癌的放射治疗提供新的靶点与策略。

放射治疗是食管癌的主要治疗手段之一，放射野内肿瘤复发及远处转移是治疗失败主要原因。上皮间质转化（EMT）增加了肿瘤细胞对放射治疗的抗性并与放疗后肿瘤复发密切相关。Snail是EMT的关键转录因子并参与肿瘤的放射抵抗。HuR是一种mRNA 结合蛋白，广泛参与基因的转录后调节，但是否参与食管癌放射敏感性调节尚不清楚。本项目组前期研究发现HuR可调节Snail蛋白的表达并影响放射引起的食管癌细胞的凋亡和克隆形成。本课题拟在前期预实验基础上运用生化、细胞学技术，在细胞和动物模型上研究1）HuR通过转录后调控Snail影响食管癌EMT过程的分子机理；2）在细胞水平和动物水平阐明HuR通过Snail调节EMT对食管癌放射敏感性的影响。通过上述研究，阐述HuR/Snail通路调控食管癌放射敏感性的新机制，为食管癌的放射治疗提供新的靶点与策略。