前期发现，乳腺癌组织和乳腺癌干细胞(BCSC)中HOTAIR高表达，miR-502低表达；乳腺癌中TRAF2高表达，并与TRAF4结合影响TRAF4核浆分布；软件预测到HOTAIR与miR-502、miR-502与TRAF2 3’UTR间有结合位点。推测BCSC中HOTAIR高表达，miR-502低表达，HOTAIR结合miR-502并减弱其对TRAF2的负性调控，影响TRAF2与TRAF4互作以及BCSC的生物学行为。我们拟先验证HOTAIR与miR-502结合，负性调控miR-502影响BCSC生物学行为的机制；进一步研究miR-502与TRAF2结合作用；明确miR-502通过TRAF2影响TRAF2与TRAF4互作，进而影响BCSC生物学行为的机制。最后在BCSC裸鼠移植瘤模型中研究HOTAIR抑制剂与miR-502单独或联合应用对TRAF2和TRAF4基因功能的调控作用及抑瘤效应

Our previous research showed that HOTAIR was high expression in breast cancer tissues and stem cells(BCSC),while the expression of miR-502 was low ; TRAF2 was high expression in breast cancer and it could bind TRAF4 ,then regulating the cytoplasmic/nuclear distribution of TARF4;we found that there are binding sites between HOTAIR and miR-502,miR-502 and TRAF2 3’UTR by bioinformatics software. We consumed that HOTAIR was high expression in BCSC, while miR-502 was low expression.HOTAIR bound miR-502 and weakened its negative regulation on TRAF2, which influenced the interaction between TRAF2 and TRAF4 and the biological behavior of BCSC. In this study, firstly we want to identify that HOTAIR bind miR-502 and negatively regulate miR-502, which influence the biological behavior of BCSC. Secondly, we will investigate the interaction between miR-502 and TRAF2. Then we will identify that miR-502 could influence the interaction between TRAF2 and TRAF4 through its regulatory effect on TRAF2. At last we will construct breast cancer stem cells transfected with pSilence-2.1-HOTAIR, which overexpressed miR-502 or not. The cells will be cultured in vitro and then be transplanted to nude mice to identify the moderating effect on the interaction of TRAF2 and TRAF4 and to the biological behaviour of breast cancer stem cells.