长链非编码RNA(lncRNA)是表观遗传学最值得关注的领域，与肿瘤发生发展的关系日益凸显,但lncRNA对多发性骨髓瘤（MM）的调控机制，仍无报道。我们借助生物信息学方法已筛选MM差异lncRNA表达谱，发现4个lncRNA分子GAS5、CRNDE、lncRNA LOC400657、PMS2P3可作为独立因素与MM不良预后相关,并可能介导DNA损伤通路上的Chk1、Chk2分子发挥功能（将在国际会议交流）。因此，本研究将以影响预后的4个lncRNA分子介导的DNA损伤通路为切入点，通过体内、体外实验探索其是否通过靶向Chk1/Chk2分子发挥调控功能，并借助RNA免疫沉淀，RNA 酶保护实验，免疫电镜等方法确认lncRNA与靶向Chk1、Chk2分子的调控模式，阐明4个lncRNA参与MM的发生、发展，以及能否为治疗提供靶点,从而为丰富理论认识和指导临床实践开拓新的领域和空间。

Long non-coding RNAs (lncRNAs) are emerging as an important class of regulatory transcripts that are implicated in a variety of biological functions in turmor, which has become the area of concern in ncRNA field. However, there is still unknown the mechanism of lncRNA in multiple myeloma (MM). Our previous work has been identified the lncRNA expression pattern and found the distinct four lncRNAs,including GAS5, CRNDE, lncRNA LOC400657, and PMS2P3, which could effect the prognosis and are highly susceptible to mediate DNA damage pathway (Du J et al. the 14th International Myeloma Workshop, IMW2013, Abstract No.147. April 2013, Tokyo, Japan). Therefore, we intend to explore deep regulation function mechanism of the four important lncRNAs mediated DNA damage pathway in vitro and in vivo. To explore the regulation model of lncRNA target Chk1, Chk2 genes in DNA damage pathway, to identify the rgulation model between lncRNA and Chk1, Chk2 by RIP, RPA, immuno-electron microscope assays, and to demonstrate the role of 4 lncRNAs in MM development. This study will demonstrate the molecular mechanism and thus lay the foundation for further research and explore promising treatment regimens.