LncRNA作为急性单核细胞白血病分子标志物的验证及其调控功能研究

项目名称： LncRNA作为急性单核细胞白血病分子标志物的验证及其调控功能研究

项目编号： No.81500126

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： 王彩霞

作者单位： 广州医科大学

项目金额： 18万元

中文摘要： 项目申请者在主持的广东省科技项目中开展了急性单核细胞白血病（M5）中长链非编码RNA(LncRNA)的研究，发现M5患者中存在LncRNA差异表达谱，而LncRNA-ENST00000414355和LncRNA-ENST00000446135在M5患者异常高表达，并能调控DNA损伤和修复通路。本项目拟运用LncRNA过表达技术、沉默技术、全基因测序、RNA pulldown、c-KLAN技术和表遗传逆转等方法，在M5细胞株U937和THP-1中探明这两LncRNA在DNA损伤、DNA修复和表观遗传（DNA甲基化和组蛋白乙酰化）中的调控功能和分子机制。我们将进一步在M5患者中探明这两LncRNA与AML-M5发病及预后的关系，探索LncRNAs作为诊断和预后新分子标志物的可行性。本项目为探索LncRNA在M5发病机制、靶向治疗和预后判断中的作用提供新的思路。

中文关键词： 急性单核细胞白血病；长链非编码RNA；分子标志；调控功能；表观遗传学

英文摘要： We previously performed series of researches on LncRNAs in acute monocytic leukemia(AML-M5) supported by the grant of Science and Technology Planning Project of Guangdong Province and found that clusters of lncRNAs were aberrantly expressed.LncRNA-ENST00000414355 and LncRNA-ENST00000446135 were highly expressed in acute monocytic leukemia patients , indicating their important regulatory roles in DNA damage and DNA repair pathway. The goal of this current project is to investigate the target genes of LncRNA-ENST00000414355 and LncRNA-ENST00000446135 and their regulatory function in DNA damage, DNA repair and epigenetic modula-tion (DNA methylation and acetylation) through analysis of LncRNA over expression, sequencing techniques, RNA pulldown, c-KLAN, and epigenetic reversal techniques in AML-M5 cell strains U937 and THP-1. Furthermore, we will investigate the potentials of using these two LncRNAs as new molecular markers in AML-M5, concerning its diagnosis, pathogenesis,targeted therapies and analysis of prognosis.

英文关键词： acute monocytic leukemia;LncRNA;molecular marker;regulatory function;epigenetics