IL-17经miR-23b促进舌鳞状细胞癌发生和发展的机制研究

项目名称： IL-17经miR-23b促进舌鳞状细胞癌发生和发展的机制研究

项目编号： No.81472527

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 彭歆

作者单位： 北京大学

项目金额： 80万元

中文摘要： 近年来发现促炎因子IL-17在多种恶性肿瘤中表达增加，提示IL-17可能是参与肿瘤发生发展的新危险因子，但IL-17在舌鳞状细胞癌(舌癌)中的作用尚不了解。我们的预实验显示舌癌患者血清及肿瘤组织IL-17表达升高，而miR-23b表达降低。本课题拟以IL-17/miR-23b通路为重点，对舌癌患者及健康志愿者进行病例对照研究，分析血清、肿瘤局部IL-17/miR-23b含量与舌癌临床病理指标的关系，从整体和组织水平揭示IL-17在舌癌发生发展中的作用。在体外培养的舌癌细胞系观察IL-17对肿瘤细胞生物学行为的影响；采用药理学及基因转染技术在细胞和分子水平上探讨miR-23b及其上下游分子NF-κB、ZEB1和MMP2在IL-17介导的舌癌细胞增殖和迁移中的作用。该项目将有助于加深对IL-17和miR-23b在舌癌发病机制中作用的认识，也为舌癌的诊断和治疗提供新的思路和药物靶点。

中文关键词： C01_口腔肿瘤；白介素17；舌鳞状细胞癌；miR-23b；核转录因子kB

英文摘要： Recent studies have revealed that interleukin 17(IL-17) is upregulated in numerous malignant tumors and suggested that IL-17 is a novel risk factor of tumor development. However, the role of IL-17 in tongue squamous cell carcinoma (TSCC) is largely uncovered. Our preliminary results show that IL-17 is elevated in both serum and local tumor tissue of TSCC patients. In contrast, the expression level of miR-23b is opposite regulated. This proposal will emphasize on the study of IL-17/miR-23b signaling pathway during the progression of TSCC. We will first explore the potential roles of IL-17 in TSCC patients, through analyzing serum and local IL-17/miR-23b levels and their relationships with clinicopathological factors of TSCC. Next, to examine the biological roles and molecular mechanisms of IL-17/miR-23b at cellular level, we will treat the cultured TSCC cell lines with pharmacological agonist/inhibitors or gene overexpression, followed by testing the roles of miR-23b as well as its signal pathway molecules-NF-κB, ZEB1, and MMP2 in IL-17-mediated TSCC proliferation and migration. Our study will provide in-depth knowledge to the current understanding of IL-17 and miR-23b in TSCC development, and give insight to novel diagnostic and therapeutic target for TSCC.

英文关键词： mouth neoplasms;interleukin-17;tongue squamous cell carcinoma;miR-23b;nuclear factor kB