我们发现长链非编码RNA AFAP1-AS1在鼻咽癌中表达上调且与不良预后相关，但其功能和机制还鲜有研究；体内外实验证实敲低AFAP1-AS1可影响细胞骨架重构，抑制侵袭和迁移；利用蛋白组学技术发现Rho/Rac通路多个分子表达改变；结合临床资料分析、CHIP-Seq、RNA pull-down及生物信息学预测，本项目提出了“MYC及SWI/SNF染色质重构复合物共同调控AFAP1-AS1的转录，转录出的AFAP1-AS1 RNA又作为SWI/SNF复合物的组分之一，影响SWI/SNF复合物的组装和活性，进而调节Rho/Rac通路多个关键分子的表达，Rho/Rac通路则通过调控微管微丝组装和细胞骨架重构，促进鼻咽癌细胞的侵袭和转移”这一假说。本项目将初步明晰AFAP1-AS1在MYC-SWI/SNF-Rho/Rac信号通路中的表达调控规律，并阐释它在鼻咽癌发生发展中的作用和机制。

In our previous projects, we have found that a long non-coding RNA, termed AFAP1-AS1, is overexpressed in nasopharyngeal carcinoma and that AFAP1-AS1 levels predict poor outcomes; however, the biological function of AFAP1-AS1 and its mechanism are largely unknown. We have further elucidated that knock-down of AFAP1-AS1 could inhibit invasion and migration of nasopharyngeal carcinoma cells by regulating the assembly of microtubules and microfilaments, and the reorganization of the cytoskeleton, both in vivo and in vitro. Using a proteomics strategy, we have also shown that several key molecules of the Rho/Rac signaling pathway were significantly dysregulated in cancer cells by knock-down of AFAP1-AS1. In light of these findings, clinical data analysis of a large cohort of cancer patients, the results of our CHIP-sequencing and RNA pull-down experiments, and bioinformatics prediction, we hypothesize that the well-known oncogene MYC and the SWI/SNF chromatin remodeling complex regulate the transcription of the AFAP1-AS1 gene. Acting as a component of the SWI/SNF complex, transcribed AFAP1-AS1 RNA affects the organization of the SWI/SNF complex, modulates SWI/SNF genomic binding, and antagonizes the SWI/SNF-mediated regulation of multiple genes of the Rho/Rac signaling pathway; in turn, the Rho/Rac signaling pathway regulates the assembly of microtubules and microfilaments, and the reorganization of the cytoskeleton, thus promoting invasion and migration of cancer cells. In this study, we aim to elucidate in detail the role and mechanism of AFAP1-AS1 in promoting nasopharyngeal carcinoma progression through regulating MYC-SWI/SNF-Rho/Rac gene signaling transduction.