miR-143/miR-145与TLR4-NF-κB组成的信号调控网络在口腔鳞癌中的作用研究

项目名称： miR-143/miR-145与TLR4-NF-κB组成的信号调控网络在口腔鳞癌中的作用研究

项目编号： No.91229103

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 陈万涛

作者单位： 上海交通大学

项目金额： 85万元

中文摘要： 非可控性炎症（nonresolving inflammation, NRI）参与了癌症的发生、发展、浸润转移和放化疗抵抗等病理过程。NRI与癌症之间关系和调控机制的阐明，有助于癌症病因的明确和治疗策略的发展。申请人前期研究发现，在口腔黏膜癌变和发展过程中存在microRNAs表达谱的变化；与炎症和免疫相关的Toll样受体信号通路也发挥了调控作用；生物信息学分析结果还提示，miR-143与miR-145簇对炎症相关的主要信号通路TLR4和NF-κB都具有靶向调控作用。本项目拟采用国际上公认的NRI恶性转化疾病模型-扁平苔癣类癌前病变和口腔鳞癌，针对癌发生和发展的关键过程，综合利用系统生物学技术，在表观遗传学和遗传学两个层面，动态解析口腔黏膜NRI和口腔鳞癌之间存在的必然联系，确定NRI恶性转化的基本调控网络以及促使癌变的关键节点和作用因子，为该类癌的诊断和治疗提供有价值的候选靶点。

中文关键词： 口腔黏膜鳞癌；microRNA；调控网络；靶基因；炎症因子

英文摘要： The nonresolving inflammation (NRI) is involved in the multisteps of cancer development, such as tumorigenesis, cancer progression, invasion, metastasis, and resistance to radiation and chemotherapy. The clarification of the relationship and regulatory mechanism between NRI and cancer is helpful to understand cancer aetiology and to develop new anti-cancer treatment strategies. Our preliminary studies showed that the microRNA expression patterns varied in different periods of oral squamous cell carcinoma (OSCC) development. In addition, the Toll-like receptor signal pathway which associates with inflammation and immune also plays a critical role in transformation from NRI to OSCC. Bioinformatics analysis also suggested that miR-143 and miR-145, which belong to the same miRNA cluster, could negatively modulate the expression of some key molecules of TLR4/NF-κB signaling pathway. This study intends to adopt internationally recognized NRI malignant transformation disease model -Lichen planus and OSCC. Based on the Systems biology technology, the relationship between NRI and OSCC at both genetic and epigenetic levels may be dynamically determined. Identification of the molecular mechanism of malignant transformation of NRI lesion could provide some novel anti-cancer strategies and effective candidate targets to tre

英文关键词： Oral squamous cell carcinoma；microRNA；regulatory network；targeted gene；inflammation factor