肿瘤相关性中性粒细胞通过上调肝癌细胞miR-301b-3p促进肝癌侵袭转移的机制研究

项目名称： 肿瘤相关性中性粒细胞通过上调肝癌细胞miR-301b-3p促进肝癌侵袭转移的机制研究

项目编号： No.81502485

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： 周少来

作者单位： 复旦大学

项目金额： 20万元

中文摘要： 最近研究表明肿瘤微环境中浸润的中性粒细胞在肿瘤发生发展过程中起到至关重要的作用。前期工作中，我们发现肿瘤相关性中性粒细胞(TANs)可以促进肝癌的生长和转移；通过microRNA测序及细胞功能试验筛选并证实miR-301b-3p是参与TANs促进肝癌细胞增殖，迁移，和侵袭的关键microRNA。本课题拟首先通过裸鼠成瘤试验，明确miR-301b-3p在TANs促进肝癌侵袭和转移过程中的重要作用；然后通过生物信息学预测及基因芯片筛选并验证该microRNA的靶基因，进而通过体内外实验明确靶基因在miR-301b-3p介导的TANs促进肝癌进展过程中的作用；最后在肝癌组织样本中观察TANs、miR-301b-3p和靶基因的表达及和肝癌患者预后的相关性。通过以上研究，明确肝癌微环境中TANs通过上调肿瘤细胞miR-301b-3p，促进肝癌侵袭转移的作用机制，为探讨肝癌治疗中新的干预靶点提供依据。

中文关键词： C09_肝和肝内胆管肿瘤；肿瘤微环境；肿瘤相关性中性粒细胞；小RNA；转移

英文摘要： Tumor-associated neutrophils (TANs) play a crucial role in carcinogenesis and cancer progression. We have revealed that TANs from Hepatocellular carcinoma (HCC) microenvironment have capability to promote HCC growth and metastasis. Through microRNA-seq and cell functional analysis, we screened and validated that miR-301b-3p played a crucial role on TANs-enhanced the proliferative, migratory and invasive ability of HCC cells. In this study, we firstly plan to identify the crucial role of miR-301b-3p on TANs-promoted HCC invasion and metastasis in xenograft nude mouse models. Then, through bioinformatics prediction and gene chips analysis, we will screen and identify the target gene(s) of this microRNA; and demonstrate the roles of this/these gene(s) on miR-301b-3p mediating TANs-promoted HCC progression by in vitro and in vivo study. Finally, using tissue microarrays (TMAs) of HCC samples, we will determine the relationship between TANs, miR-301b-3p and the target gene(s), and evaluate their prognostic significance. Through the above research, we will determine the effect and mechanism of TANs in inducing miR-301b-3p to promote the invasion and metastasis of HCC, and provide experimental evidence for exploring the new intervention targets on the metastasis and recurrence of HCC.

英文关键词： Liver and intrahepatic bile duct tumor;tumor microenvironment;TANs;microRNA;metastasis