Loss of long noncoding RNA FOXF1-AS1 regulates epithelial-mesenchymal transition, stemness and metastasis of non-small cell lung cancer cells
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Liyun Miao1,*, Zhen Huang3,*, Zhang Zengli4, Hui Li1, Qiufang Chen5, Chenyun Yao6, Hourong Cai1, Yonglong Xiao1, Hongping Xia2, Yongsheng Wang1
1Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China
2Department of Pathology, Sir Run Run Hospital & Nanjing Medical University, Nanjing 211166, China
3Department of Laboratory Medicine, Longgang District Central Hospital, Longgang District, Shenzhen, Guangdong 518116, China
4Department of Respiratory Diseases, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
5Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
6Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing 210009, China
*These authors have contributed equally to this work
Yongsheng Wang, email: [email protected]
Hongping Xia, email: [email protected]
Keywords: LncRNA, FOXF1-AS1, EMT, metastasis, lung cancer
Received: April 22, 2016 Accepted: August 11, 2016 Published: August 26, 2016
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.
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