Bo Hao, Fan Liqing, Li Jingjing, Liu Zhizhong, Zhang Shanshan, Shi Lei, Guo Can, Li Xiayu, Liao Qianjin, Zhang Wenling, Zhou Ming, Xiang Bo, Li Xiaoling, Li Guiyuan, Xiong Wei, Zeng Zhaoyang, Xiong Fang, Gong Zhaojian
The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
J Cancer. 2018 Nov 24;9(24):4677-4683. doi: 10.7150/jca.26461. eCollection 2018.
Long non-coding RNAs (lncRNAs) are dysregulated in various cancers. However, the clinical relevance and functional roles of AFAP1-AS1 in colon cancer (CC) have not been clarified. We analyzed the lncRNA expression patterns in Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) RNA-seq datasets, and found that the expression level of AFAP1-AS1 was significantly elevated in CC tissues. High levels of AFAP1-AS1 were associated with poor disease-free survival and overall survival in CC patients. experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the cell invasive and migration capability in CC cell line HT-29. AFAP1-AS1 knockdown also increased the expression of E-cadherin and ZO-1 while inhibited the expression of Vimentin, MMP9, ZEB1 and β-catenin, suggesting that AFAP1-AS1 is involved in the epithelial-mesenchymal transition (EMT) process of CC. Further studies confirmed that AFAP1-AS1 knockdown also affected the actin-cytokeratin signaling pathway. Thus, AFAP1-AS1 might be a potential novel diagnostic marker and therapeutic target for CC.
长链非编码RNA（lncRNAs）在多种癌症中表达失调。然而，AFAP1-AS1在结肠癌（CC）中的临床相关性和功能作用尚未阐明。我们分析了基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）RNA测序数据集中的lncRNA表达模式，发现AFAP1-AS1在CC组织中的表达水平显著升高。CC患者中高水平的AFAP1-AS1与无病生存期和总生存期较差相关。实验表明，敲低AFAP1-AS1可显著抑制CC细胞系HT-29的细胞侵袭和迁移能力。敲低AFAP1-AS1还增加了E-钙黏蛋白和ZO-1的表达，同时抑制了波形蛋白、基质金属蛋白酶9、锌指蛋白E盒结合因子1（ZEB1）和β-连环蛋白的表达，提示AFAP1-AS1参与了CC的上皮-间质转化（EMT）过程。进一步研究证实，敲低AFAP1-AS1也影响了肌动蛋白-细胞角蛋白信号通路。因此，AFAP1-AS1可能是CC潜在的新型诊断标志物和治疗靶点。
