长链非编码RNA-ANRIL在人类T淋巴细胞白血病1型病毒致癌中的作用及其分子机制研究

项目名称： 长链非编码RNA-ANRIL在人类T淋巴细胞白血病1型病毒致癌中的作用及其分子机制研究

项目编号： No.31470262

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 赵铁军

作者单位： 浙江师范大学

项目金额： 85万元

中文摘要： 人类T淋巴细胞白血病1型病毒（HTLV-1）的感染与成人T细胞白血病（ATL）的发生密切相关，然而目前对HTLV-1致癌机制仍缺乏全面了解。最近的研究表明长链非编码RNA（lncRNA）在肿瘤发生过程中发挥着重要的作用。然而lncRNA在HTLV-1致癌中的调控功能尚未有报导。我们前期使用lncRNA芯片筛选得到ATL细胞株中差异表达的lncRNA，并锚定关键性lncRNA-ANRIL。预实验发现沉默ANRIL后，白血病细胞的恶性增生受到抑制，且抑癌基因p16的表达显著上调。因此我们推测在ATL中，异常表达的ANRIL通过阻遏抑癌基因的表达，从而导致了白血病的发生。据此，本项目拟利用荧光素酶报告系统，RNAi，免疫沉淀等技术，从体外细胞水平和体内实验动物水平研究ANRIL在HTLV-1致癌过程中的功能及调控机制。该研究将为阐明HTLV-1致癌机理提供新思路，并为治疗ATL提供新靶点。

中文关键词： 人类T淋巴细胞白血病1型病毒；长链非编码RNA；ANRIL

英文摘要： Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), while the molecular mechanism of HTLV-1 mediated leukemogenesis is still unknown. Accumulating evidences show that long non-coding RNA (lncRNA) plays a critical role in the development of multiple cancers by regulating intracellular signal transduction. However, the function of lncRNA on HTLV-1-induced oncogenesis has not been elucidated. Our pilot study indicated the aberrant expression profiles of lncRNAs in HTLV-1 associated cell lines. In addition, when the expression of ANRIL, a lncRNA which is upregulated in ATL cells, was knocked down, the proliferation of leukemic cells was blocked. Moreover, inhibition of lncRNA-ANRIL restored the expression of tumor suppressor protein, p16. Thus, we hypothesize that lncRNA-ANRIL may support proliferation of ATL cells by inhibiting tumor suppressor gene. In this project, we will study the function of lncRNA-ANRIL in ATL using various methods, such as luciferase assay, RNA interference, immunoprecipitation etc, and clarify the molecular mechanism by which ANRIL promotes ATL cell proliferation and tumorigenesis in vitro and in vivo. This research may provide new insights into the mechanism of oncogenesis by HTLV-1, and implicate lncRNA-ANRIL as potential therapeutic target.

英文关键词： HTLV-1;lncRNA;ANRIL