长非编码RNA HULC在细胞转录调控中的作用及其分子机制研究

项目名称： 长非编码RNA HULC在细胞转录调控中的作用及其分子机制研究

项目编号： No.31470756

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： 张晓东

作者单位： 南开大学

项目金额： 80万元

中文摘要： 调节性RNAs是近年来国际研究的热点，在基因表达调控中发挥重要作用。长非编码RNAs是调节性RNAs的重要组成部分，广泛参与生理和病理功能。长非编码RNA HULC因在肝癌细胞中高表达而命名,申请者前期研究发现HULC具有促进肝癌细胞增殖的作用，在此基础上，基于HULC参与转录调控的假说，本课题以正常肝细胞和肝癌细胞为研究模型，主要研究：（1）探讨HULC在肝癌细胞脂类代谢异常中对重要脂类代谢酶ACSL1的调节作用及其分子机制；（2）探讨HULC在促肝癌细胞血管形成中对SPHK1的调节作用及其分子机制；（3）探讨HULC 在促进肝癌细胞有丝分裂中对节律蛋白的调节作用及其分子机制。实验中拟应用分子克隆、细胞培养、RNA干扰和报告基因等分子生物学技术，并结合临床手术标本验证其在肝癌组织中表达的相关性，进而详细阐明其作用的分子机制。该研究将揭示长非编码RNA在细胞转录调控中的生理病理学意义。

中文关键词： 分子生物学；相互作用；转录调控；转录因子；细胞周期调控

英文摘要： The investigation of regulatory RNAs is the international hot point.They display an important roles in gene expression and regulation. Long non-coding RNAs are one of key components of regulatory RNAs and widely involved in the physiological and pathological functions in the cells. Highly up-regulated in liver cancer (HULC), a long non-coding RNA, was termed due to its highly expressed in hepatoma cells. We previously found that HULC promoted the proliferation in hepatoma cells. Based on the hypothesis that HULC regulates transcription of cells,in this study using human normal liver cells and hepatoma cells as models we are going to conduct the researches, such as: (1)investigate the effect of HULC on the regulation of key lipid metabolism enzyme ACSL1 in hepatoma cells;(2)research the effect of HULC on SPHK1 in angiogenesis of hepatoma ;(3) study the effect of HULC on cell mitosis in regulating clock protein. In the experiments, we will use the molecular biology technologies, such as molecular cloning, cell culture, RNA interference and reporter gene assays, combining the application of clinical HCC samples for validating the relative expression of HULC to ACSL1 (SPHK1, clock protein), to explore the mechanism of HULC in transcriptional regulation.Thus,our study will contribute to the significance of physiology and pathology of HULC in transcriptional regulation of cells.

英文关键词： Molecular-biology;Interaction;Transcriptional regulation;Transcriptional factor;Cell cycle regulation