细胞内信号网络的动态变化决定肿瘤的发生和发展，寻找能同时调控多重信号通路的关键基因对于肿瘤靶向治疗具有重要意义。长链非编码RNA(lncRNA)可通过调控癌基因和抑癌基因表达，影响肿瘤的恶性演进。然而，lncRNA调控细胞内信号网络的机制尚不明确。申请人前期研究鉴定出一个全新的lncRNA AC012181.2，发现干扰其表达可抑制口腔癌增殖和侵袭转移，并诱导细胞凋亡。我们提出：AC012181.2通过激活PI3K-Akt、FGF19-FGFR4通路及下游信号因子，上调口腔癌的增殖和抗凋亡活性；并通过调控DCN-TGF-β通路及下游信号因子，诱导口腔癌发生EMT和侵袭转移。本课题拟通过信号通路检测、增殖及凋亡相关因子分析、EMT标志物检测、体内和体外生物学效应评估等手段，从分子、细胞和整体水平探讨AC012181.2通过调控细胞内信号网络促进口腔癌恶性演进的分子机制，为肿瘤治疗提供新靶点。

The dynamic changes of intracellular signaling network determine the occurrence and development of cancer. It is of great importance for targeted cancer therapy to search the key gene which could simultaneously regulate multiple signaling pathways. Long non-coding RNA (lncRNA) modulates the malignant progression of cancer via regulating the expression of oncogenes and anti-oncogenes. However, the molecular mechanisms of lncRNA-regulated intracellular signaling network remain elusive. The applicant identified a novel lncRNA AC012181.2 in the previous study. We discovered that AC012181.2 inhibition resulted in prohibited proliferation and invasion, and promoted apoptosis in oral cancer. We therefore propose the hypothesis that AC012181.2 could promote cell proliferation and invasion by activating PI3K-Akt pathway and FGF19-FGFR4 pathway in oral cancer. Meanwhile, AC012181.2 could also induce EMT and metastasis by regulating DCN-TGF-β pathway in oral cancer. In this project, we will test the activation of signaling pathways, analyze the expression of proliferative and apoptotic factors, examine EMT markers expression, and investigate in vivo and in vitro biological effects. We plan to identify the mechanisms that AC012181.2 promote the malignant progression by regulating intracellular signaling network. These results will provide a new target for cancer therapy.