随着基因组学研究的深入，近年来长非编码RNA（lncRNA）在肿瘤相关调控网络中的重要性逐渐凸显。课题组前期研究发现lncRNA-DLEU2在胃癌组织中显著上调且与预后相关，过表达DLEU2可促进胃癌细胞的增殖及迁移能力；进一步研究发现DLEU2可与具有促癌功能的MUC4蛋白结合，且DLEU2可能通过MUC4影响ErbB2磷酸化而发挥促癌功能。基于此，我们提出假说：DLEU2通过结合MUC4介导ErbB2发生磷酸化，促进生长信号向下游传导，刺激细胞增殖转移。本项目拟进一步通过体内外生物学实验方法明确DLEU2在胃癌中的功能并结合分子生物学实验阐明DLEU2/MUC4/ErbB2调控轴在胃癌恶性生物学行为的作用机制；同时检测临床样本中该调控轴关键分子的表达，并确定其与胃癌患者临床病理参数及预后相关性。本项目对于筛选可用于胃癌预后评估及靶向治疗的分子标记物具有重要的理论意义和临床价值。

In recent years, along with the development of genomics research, the importance of long non-coding RNA (lncRNA) in tumor related regulation network become more and more prominent. In our previous study, we identified that lncRNA-DLEU2 was significantly upregulated in gastric cancer (GC); and patients with higher DLEU2 expression levels had poorer prognosis. Further in vitro functional assays attested that DLEU2 upregulation of GC cells could lead to a more aggressive biological feature, manifested as promoted cancer cell proliferation and migration. However, the real function of DLEU2 in GC and the underlying regulatory mechanism still need to be clarified. In further investigating the underlying mechanism, we identified MUC4 as the binding target of DLEU2, and DLEU2 may play the role of promoting cancer through the effect of MUC4 on the phosphorylation of ErbB2. There might be a DLEU2-MUC4-ErbB2 signaling pathway which plays an important role in gastric cancer progression. Based on these results, we proposed the potential mechanism hypothesis that DLEU2 prompt of the development and progression of GC by DLEU2-MUC4-ErbB2 signaling pathway. This project plans to investigate the biological function of DLEU2 in the onset and development of GC, and to clarify the downstream regulative mechanism related to its biological function by using a serious of biological experimental assays. This study will offer important theoretical significance and clinical value in screening molecular markers for prognosis and targeted therapy of GC.