miR-34c-5p在鼻咽癌转移中的作用和机制研究

Distant metastasis is a key factor restricting to improve curative effect of nasopharyngeal carcinoma. Thus, there is a need to identify metastasis-related factors and clarify its function and mechanism, in order to guide clinical selection of high risk patients for individual therapy, so as to achieve the goal of improve curative effect. Our previous study found that: ① a set of 11 miRNAs could accurately distinguish patients with high metastasis potential from patients with low metastasis potential, among them miR-34c-5p was obviously decreased in patients with high metastasis potential. ② miR-34c-5p inhibits cell migration and invasion of nasopharyngeal carcinoma, and MET was predicted to be the target of miR-34c-5p. On the basis of the preliminary experiment, we put forward the hypothesis that miR-34c-5p inhibits cell migration, invasion and metastasis by targeting MET in patients with nasopharyngeal carcinoma. This project is proposed on the basis of the scientific hypothesis, which would first clarify the function and mechanism of miR-34c-5p in nasopharyngeal carcinoma, and evaluate its value in predicting distant metastasis. Through the implementation of this project, it can provide new targets for the treatment of nasopharyngeal carcinoma, and further guide clinical selection of high risk patients for individual treatment.

远处转移是制约鼻咽癌疗效提高的关键因素。只有鉴定出与鼻咽癌转移相关的因素，系统阐明其作用和机制，才能指导临床甄选出高转移风险患者进行个体化治疗，从而达到提高疗效的目的。我们前期研究发现：①一组11个miRNA可准确地区分转移和非转移鼻咽癌，其中miR-34c-5p在转移鼻咽癌组织中表达明显降低；②miR-34c-5p可抑制鼻咽癌细胞的迁移和侵袭，生物信息学分析发现MET是其调控靶点。在此预实验基础上，我们提出假说：miR-34c-5p通过靶向MET基因抑制鼻咽癌细胞的侵袭和转移，可预测鼻咽癌患者发生远处转移的风险。本项目拟在此科学假说的基础上，首次揭示miR-34c-5p在鼻咽癌转移中的作用和机制，并明确其在鼻咽癌远处转移预测中的价值，通过本项目的实施，可为鼻咽癌治疗提供新的靶点，并指导临床甄选出高转移风险患者进行个体化治疗。

远处转移是制约鼻咽癌疗效提高的关键因素。只有鉴定出与鼻咽癌转移相关的因素，系统阐明其作用和机制，才能指导临床甄选出高转移风险患者进行个体化治疗，从而达到提高疗效的目的。在本课题的资助下，我们课题组取得了如下成果：①阐明了miR-34c-5p、miR-93、miR-320b、miR-101、miR-16、miR-143、miR-145共7个miRNA在鼻咽癌生长增殖以及侵袭转移中的具体功能和分子机制，这不仅可以帮助更好地理解鼻咽癌恶性进展的分子机理，而且可以为鼻咽癌治疗提供潜在的治疗靶点，特别是为将来以miRNA为基础设计的小分子靶向治疗药物在鼻咽癌的应用奠定了理论基础；②发现了一组13个基因构成的分子标签可以预测鼻咽癌患者的无远处转移生存，并首次基于基因表达谱和N分期等临床预后因素构建了鼻咽癌的Nomogram预后模型，可以帮助筛选出高转移风险的鼻咽癌患者，从而有效地指导鼻咽癌临床个体化治疗的开展。申请人以（共同）通讯作者身份发表SCI收录论文9篇，总IF 74.952，包括Lancet Oncol（IF 33.9）、Cancer Lett（IF 6.375）、Cell Death Dis（IF 5.965）等，并作为成员获得了2016年度广东省南粤创新奖“中山大学广东癌（鼻咽癌）研究诊治团队”。