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

// Liyun Miao 1, * , Zhen Huang 3, * , Zhang Zengli 4 , Hui Li 1 , Qiufang Chen 5 , Chenyun Yao 6 , Hourong Cai 1 , Yonglong Xiao 1 , Hongping Xia 2 , Yongsheng Wang 1 1 Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China 2 Department of Pathology, Sir Run Run Hospital & Nanjing Medical University, Nanjing 211166, China 3 Department of Laboratory Medicine, Longgang District Central Hospital, Longgang District, Shenzhen, Guangdong 518116, China 4 Department of Respiratory Diseases, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China 5 Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China 6 Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing 210009, China * These authors have contributed equally to this work Correspondence to: Yongsheng Wang, email: dolphin8012@yahoo.com Hongping Xia, email: xiahp82@gmail.com Keywords: LncRNA, FOXF1-AS1, EMT, metastasis, lung cancer Received: April 22, 2016     Accepted: August 11, 2016     Published: August 26, 2016 ABSTRACT 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.