肝癌相关巨噬细胞外泌体中lncRNA的研究

项目名称： 肝癌相关巨噬细胞外泌体中lncRNA的研究

项目编号： No.31500663

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 张秀丽

作者单位： 中国科学院北京基因组研究所

项目金额： 20万元

中文摘要： 作为人类基因组转录本的重要组成之一，LncRNAs在单核-巨噬细胞和T细胞等免疫细胞中表达十分活跃，并且在免疫细胞分化和免疫调节中发挥重要作用。研究表明，肝脏中的固定性巨噬细胞——枯否细胞，在肝癌微环境中可被驯化为肿瘤相关巨噬细胞（Tumor Associated Macrophages，TAMs）；而这些细胞则可以通过外泌体、细胞因子等细胞间通讯方式，促进肿瘤生长、侵袭与转移。虽然外泌体中的lncRNAs在近年来屡有报道，但其在肝癌相关巨噬细胞外泌体中的分布和功能尚不为人所知。本项目将利用高通量测序等技术，在肝癌相关巨噬细胞外泌体中，鉴定并筛选出对肝癌细胞恶性转化有重要影响的lncRNAs分子，并对其整体分布规律进行系统性分阐述；此外，在对这些lncRNAs分子进行规模检测和功能探索的基础上，进一步探讨其作为肝癌分子标记物和潜在治疗靶点的可能性。本项目可以部分填补肝癌微环境研究的空白。

中文关键词： 转录组；RNA表达谱；外泌体；细胞表型；调控机制

英文摘要： LncRNA is an important component of the human genome transcript, which shows active expression in monocyte-macrophage, T cell and some other immune cells. Besides, LncRNA displays significant role in immunocyte differentiation and immune modulation. Based on previous reports, kupffer cell, the resident macrophage in liver, can be domesticated and finally become tumor associated Macrophages (TAMs) in the hepatocellular microenvironment. The latter can secrete various growth factors, exosomes and other medium of intercellular communication, regulating tumor growth, invasion and metastasis. lncRNAs in exosomes have gained attention in recent years, however, the distribution and function of lncRNAs in the exosomes released by hepacellular TAMs remain unclear. Through high throughput sequencing technology and other related technologies, this project aims to identify and screen the exosomal IncRNAs which significantly affect hepacellular malignant transformation and then systematically expound the distribution regularity. After detecting the scale and discovering the function of these IncRNAs, we will further investigate the possibilities of their acting as molecular markers and potential therapeutic targets of hepatocarcinoma. Therefore, the study can partly fill the gaps in hepacellular microenviroment research.

英文关键词： Transcriptome;RNA Expression Profile;Exosomes ;Cell Phenotype;Regulation Mechanism