新嵌合体RRM2-c2orf48诱导鼻咽癌侵袭转移的机制

近年研究表明，嵌合转录本与恶性肿瘤的发生和预后相关。我们近期发现野生型RRM2与c2orf48存在嵌合转录本，且在鼻咽癌细胞及组织中表达水平高；过表达嵌合体RRM2-c2orf48能诱导鼻咽癌细胞发生上皮间质转化(EMT)，并增强细胞的侵袭能力。此外，该嵌合体可增加Ras、p-Akt及β-Catenin通路相关蛋白的表达。提示嵌合体RRM2-c2orf48可能在鼻咽癌侵袭转移中发挥重要作用。本课题拟通过免疫组化和qPCR等方法明确嵌合体RRM2-c2orf48在鼻咽癌中的表达，并与患者临床病理特征及预后进行相关分析；通过体内外实验探讨其对鼻咽癌细胞侵袭转移能力的影响；应用通路蛋白抑制剂、RNA干扰及质谱分析等技术进行RRM2-c2orf48相关功能及机制研究，从而揭示嵌合体RRM2-c2orf48诱导鼻咽癌细胞发生EMT和侵袭转移的分子机制，为鼻咽癌分子诊断和治疗提供新思路。

Recently, chimeric transcripts are believed to be associated with the development and poor prognosis of malignant tumors. Our preliminary study showed that a novel chimera transcript of RRM2 and c2orf48 has been first found at mRNA level in C666 cell line (nasopharyngeal carcinoma ). The chimera is dramatically upregulated in cancer cell lines and cancer tissues rather than normal epithelial cells. Overexpression of chimeric RRM2-c2orf48 induced epithelial-mesenchymal transition (EMT) and increased the mobility of NPC cells in vitro assay. Furthermore, the overexpression of chimeric RRM2-c2orf48 activated certain signal pathways, such as Ras, p-Akt and β-Catenin，which indicating chimeric RRM2-c2orf48 could be important in invasion and migration of NPC.In this study, we will further convince the expression of chimeric RRM2-c2orf48 in NPC by immunohistochemistry and Real-time PCR, and analyze the relationship between the expression of chimeric RRM2-c2orf48 and the clinicopathological features and prognosis of NPC patients；then explore its influence on migration ability of nasopharyngeal carcinoma cells in vivo or vitro assay.Also,the related function and molecular mechanisms of chimeric RRM2-c2orf48 would be detected through mass spectrometry, inhibition of signaling pathways and RNA interference method. All above research could be beneficial to demonstrate the molecular mechanism of chimeric RRM2-c2orf48 inducing EMT and enhancing invasion and migratin of NPC cells, thereby providing new insight into the molecular diagnosis and therapy of NPC.