Loss of long noncoding RNA FOXF1-AS1 regulates epithelial-mesenchymal transition, stemness and metastasis of non-small cell lung cancer cells

• Published in: Oncotarget 2016-10, Vol.7 (42), p.68339-68349
• Main Authors: Miao, Liyun, Huang, Zhen, Zengli, Zhang, Li, Hui, Chen, Qiufang, Yao, Chenyun, Cai, Hourong, Xiao, Yonglong, Xia, Hongping, Wang, Yongsheng
• Format: Article
• Language: English
• Subjects: Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Self Renewal; Down-Regulation; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Epithelial-Mesenchymal Transition - genetics; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Neoplasm Metastasis; Research Paper; RNA, Long Noncoding - genetics
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.11630

Although recent evidence shows that long noncoding RNAs (lncRNAs) are involved in the regulation of gene expression and cancer progression, the understanding of the role of lncRNAs in lung cancer metastasis is still limited. To identify novel lncRNAs in non-small cell lung cancer (NSCLC), we profile NSCLC tumor and matched normal samples using GeneChip® Human Gene 2.0 ST Array, which provides the most accurate, sensitive, and comprehensive measurement of protein coding and lncRNA transcripts. We identified a panel of key factors dysregulated in lung cancer. Among them, the expression of FOXF1-AS1 was significantly downregulated in lung cancer. Stable overexpression of FOXF1-AS1 inhibits lung cancer cell migration and invasion by regulating EMT. Meanwhile, loss of FOXF1-AS1 mediates stem-like properties of lung cancer cells. Interestingly, we found that FOXF1-AS1 physically associates with PRC2 components EZH2 and loss of FOXF1-AS1 mediates cell migration and stem-like properties require EZH2. Loss of FOXF1-AS1 is also correlated with downregulation of FOXF1 in lung cancer. These results suggested that FOXF1-AS1 might regulate EMT, stemness and metastasis of NSCLC cells via EZH2, indicating it as a therapeutic target for future treatment of NSCLC.