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.
Highlights
As one of the most common causes of cancer related death of the world, lung cancer has become a severe public health problem [1]
We identified a panel of key factors dysregulated in lung cancer
Among the differentially expressed long noncoding RNAs (lncRNAs) which have already been observed, associations between HOX antisense intergenic RNA (HOTAIR), metastasis-associated- in-lungadenocarcinoma-transcript-1 (MALAT1), BRAF activated noncoding RNA (BANCR),SPRY4 intronic transcript 1 (SPRY4-IT1) and antisense noncoding RNA in the INK4 locus (ANRIL) with non-small cell lung cancer (NSCLC) have been reported, which directs that these lncRNAs may be the novel modulators in the process of metastasis in human NSCLC [14, 20,21,22,23]
Summary
As one of the most common causes of cancer related death of the world, lung cancer has become a severe public health problem [1]. The high mortality is probably related to early metastasis [8]; the mechanism underlying metastasis is still unknown yet. Metastasis of NSCLC is a complex process and modulated by many steps [9]. NSCLC cells escape from the primary tumor to a new organ or tissue when metastasis begins. The main critical changes of progression and metastasis are epithelial-to-mesenchymal transition (EMT) and cancer stemness (CS) [10, 11], which play an www.impactjournals.com/oncotarget important role in the embryonic development as well as the invasion and metastasis of cancer cells. To inhibit the process of metastasis and invasion of tumor cells seems vital to inhibit the tumor progression
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