长链非编码RNA AK126420 通过结合蛋白RSK2促进胃癌转移的作用及机制研究

长链非编码RNA（lncRNA）在肿瘤的浸润、转移中发挥重要作用。前期工作中，我们利用lncRNA芯片筛选了转移组胃癌中差异表达的lncRNA，其中AK126420在转移组胃癌中表达显著上调。我们发现AK126420在体外可促进胃癌细胞的迁移和浸润。并发现AK126420可与RSK2蛋白结合，增加RSK2的表达及磷酸化水平，并可能通过调控CREB1的磷酸化来激活VEGF、TGF-β等通路从而促进胃癌的浸润转移。在此基础上，我们拟进一步探究AK126420在胃癌中的表达情况及临床意义，通过体外、体内实验明确AK126420对胃癌迁移浸润能力的影响；采用RNA pull-down、RIP、IP、Western blot等方法验证AK126420对RSK2及CREB1的调控作用，构建AK126420/RSK2复合体-CREB1-下游信号通路调节胃癌浸润转移的信号网络。

Long non-coding RNA (lncRNA) plays an important role in tumor invasion and metastasis. In previous study, Arraystar Human LncRNA Microarray was used to screen the differential expression of lncRNAs between GC tissues with and without lymph node metastasis (LNM). And we found that AK126420 was significantly up-regulated in GC with LNM. We found that AK126420 promotes the migration and invasion of GC cells in vitro. It was found that AK126420 binds to RSK2 protein, increases the expression and phosphorylation level of RSK2, and may activate VEGF and TGFβ pathways by regulating the phosphorylation of CREB1, thereby promoting the invasion and metastasis of GC. On this basis, we intend to further explore the expression and clinical significance of AK126420 in GC, and determine the effect of AK126420 on the migration and invasion of GC through in vitro and in vivo experiments; use of RNA pull-down, RIP, Western blot, etc. methods to verify the regulation of AK126420 on RSK2 and CREB1, and construct a signal network for AK126420 / RSK2 complex-CREB1-downstream signaling pathway to regulate gastric cancer invasion and metastasis.