新候选癌基因microRNA-4707-5p促进食管鳞状细胞癌转移的作用及机制研究

项目名称： 新候选癌基因microRNA-4707-5p促进食管鳞状细胞癌转移的作用及机制研究

项目编号： No.81502056

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张江波

作者单位： 中山大学

项目金额： 18万元

中文摘要： 食管鳞状细胞癌易于发生转移，预后差。我们前期对食管鳞癌组织的全基因组测序和基因表达检测发现了miR-4707-5p的异常扩增和高表达，且其高表达与患者的不良预后及区域淋巴结转移相关。体外实验表明miR-4707-5p可显著促进食管鳞癌细胞的迁移和侵袭。尽管我们已确定miR-4707-5p可在细胞水平抑制上皮-间质转化（EMT）关键分子E-钙粘素的表达，并可上调β-catenin的水平，但其促进食管鳞癌转移的具体分子机制仍有待深入研究。本研究将采用生物信息学预测联合表达谱芯片分析的策略全面筛选miR-4707-5p与肿瘤转移、浸润相关的靶基因，特别是对肿瘤转移密切相关的EMT及Wnt/β-catenin通路有调控作用的靶基因组合，构建miR-4707-5p在食管鳞癌中的基因调控网络；并在食管鳞癌研究队列中验证靶基因及相应调控网络。以期阐明miR-4707-5p促进食管鳞癌转移的分子机制。

中文关键词： 食管鳞状细胞癌；microRNA-4707-5p；上皮-间质转化；Wnt/β-catenin信号通路；肿瘤转移

英文摘要： Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumor in China, which is prone to invasion, metastasis and poor prognosis. Our previous result of the whole genome sequencing and gene expression detection showed abnormal amplification and high expression of miR-4707-5p in ESCC tissues. More importantly, its high expression is positively related with patients’ poor prognosis and regional lymph node metastasis. In vitro experiments showed that over expression of miR-4707-5p could promote the migration and invasion abilities of ESCC cells. Our results also showed that miR-4707-5p could suppress the expression of E-cadherin, a key molecular of Epithelial-mesenchymal transition (EMT), and up-regulate the expression of total β-catenin. However, the molecular mechanism of miR-4707-5p’s metastasis-promoting function in ESCC remains unclear. In this study, bioinformatic prediction combined with mRNA expression profile detection strategy will be used to comprehensively screen metastasis related target genes of miR-4707-5p; Candidate target genes related to EMT process and/or Wnt/β-catenin pathway will get extra attention. The gene regulation network of miR-4707-5p in ESCC will be intensively investigated. Then we will test and verify the candidate target genes and the corresponding regulation network in ESCC cohort established by our research group. The objective of this study is to elucidate the molecular mechanism of miR-4707-5p’s metastasis promoting role, and to provide novel biomarker as well as potential therapeutic target for ESCC.

英文关键词： Esophageal squamous cell carcinoma ;microRNA-4707-5p;Epithelial-Mesenchymal Transition;Wnt/β-catenin signaling pathway;Metastasis