Lnc-MRPL39-2:1在鼻咽癌上皮间充质转化过程中的作用和分子机制探讨

我们前期发现，鼻咽癌组织中显著上调的lnc-MRPL39-2:1能促进鼻咽癌细胞EMT过程；位于胞浆中的lnc-MRPL39-2:1与miR-329结合，半衰期被缩短从而表达水平降低；与HuR直接结合，进而稳定JAMA mRNA，提高JAMA蛋白表达，促进EMT。据此我们首次提出：lnc-MRPL39-2:1是鼻咽癌复发和转移的关键基因之一。本项目拟通过体内外实验探讨其在鼻咽癌中生物学功能；并利用RNA pull down、质谱、RIA-Seq 等技术探讨其促进鼻咽癌EMT的分子机制；再通过临床多中心大样本检测lnc-MRPL39-2:1及其相关蛋白质、miRNA在预警鼻咽癌侵袭和转移等方面的作用。本项目将揭示lnc-MRPL39-2:1在鼻咽癌侵袭和转移中的作用机制，对鼻咽癌的治疗抵抗，远处转移及预后判断具有重要的理论价值，为鼻咽癌治疗的新靶点提供充分理论依据。

We have found that lnc-MRPL39-2:1, which is up-regulated in the nasopharyngeal carcinoma (NPC) tissue compared with adjacent non-tumor tissue, can promote the processes of EMT of NPC cells. Our studies have confirmed that lnc-MRPL39-2:1 could bind to miR-329 and decrease its expression level through reducing its half-life. The lnc-MRPL39-2:1 interactive with HuR directly to stabilization expression of JAMA which in turn promotes the NPC cells’EMT. Based on our preliminary data, we first hypothesize that lnc-MRPL39-2:1 play a vital role in the migration and invasion of NPCs. To test the hypothesis, firstly, we will explore the physiological and functional roles of lnc-MRPL39-2:1 in EMT of NPC cells by in vitro and in vivo; secondly, we will deeply detect the mechanism of in EMT of NPC cells by using RIA-seq，RNA pull down assay and mass spectrometry. Finally, the effect of lnc-MRPL39-2:1 and its related effectors will be identified by clinical multicenter sample of NPCs. From this work, the functional role of lnc-MRPL39-2:1 in the EMT of NPC and its progression will be explored and this will be helpful to discover lnc-MRPL39-2:1 as a potential therapeutic target in patients with NPCs.