长链非编码RNA BAIAP2-AS1通过调控LMP1的m6A甲基化促进鼻咽癌恶性进程的机制研究

LMP1是EB病毒编码的重要癌蛋白，与鼻咽癌的肿瘤进程密切相关。前期研究中发现LMP1存在m6A修饰，IGF2BP3作为m6A调节蛋白可与LMP1结合调控其m6A甲基化。进一步预实验发现与IGF2BP3结合的lncRNA BAIAP2-AS1（简称BA）在鼻咽癌组织中异常高表达，与患者临床分期和不良预后紧密相关，体外沉默BA可抑制鼻咽癌细胞的增殖与侵袭能力，RIP等实验结果表明BA可募集绑定IGF2BP3介导LMP1的m6A修饰。基于上述实验证据，本项目提出“lncRNA BA通过募集绑定IGF2BP3调控LMP1的m6A甲基化参与鼻咽癌恶性进程”的科学假说。本研究拟通过体内外实验验证BA促进鼻咽癌恶性进程的生物学功能，采用RNA pull-down，RIP等方法阐明BA绑定IGF2BP3调控LMP1的分子机制，结合临床样本分析BA与鼻咽癌恶性进程的相关性，为鼻咽癌治疗寻找新靶标。

LMP1 is an important oncogene encoded by Epstein-Barr virus, which is closely related to the tumor progression of NPC. In previous studies, it was found that there was m6A modification in LMP1, and IGF2BP3, as a m6A regulatory protein, could bind with LMP1 to regulate its m6A methylation. Further experiments showed that the lncRNA BAIAP2-AS1 (BA), which can bind to IGF2BP3, was highly expressed in NPC tissue and closely related to clinical stage and poor prognosis. Functional experiments indicated that silencing of Ba inhibited the proliferation and invasion of NPC cells in vitro. Rip and other experimental results showed that Ba stimulated the m6A methylation of LMP1 by recruiting IGF2BP3. Based on the above evidences, the project proposes a scientific hypothesis that "lncRNA Ba promotes nasopharyngeal carcinoma progression by stimulating m6A modification of LMP1". The purpose of this study is to verify the biological function of BA in promoting NPC malignant process through in vitro and in vivo experiments. RNA pull-down, RIP, rescue experiments and other methods were used to elucidate the molecular mechanism of Ba binding IGF2BP3 to regulate the m6A modification of LMP1. The correlation between Ba and NPC tumor progression was analyzed with clinical samples. Our project provides a new perspective target for NPC.