LINC00261 and the Adjacent Gene FOXA2 Are Epithelial Markers and Are Suppressed during Lung Cancer Tumorigenesis and Progression

Abstract

Lung cancer continues to be the leading cause of cancer-related deaths worldwide, with little improvement in patient survival rates in the past decade. Long non-coding RNAs (lncRNAs) are gaining importance as possible biomarkers with prognostic potential. By large-scale data mining, we identified <i>LINC00261</i> as a lncRNA which was significantly downregulated in lung cancer. Low expression of <i>LINC00261</i> was associated with recurrence and poor patient survival in lung adenocarcinoma. Moreover, the gene pair of <i>LINC00261</i> and its neighbor <i>FOXA2</i> were significantly co-regulated. <i>LINC00261</i> as well as <i>FOXA2</i> negatively correlated with markers for epithelial-to-mesenchymal transition (EMT) and were suppressed by the EMT inducer TGFβ. Hierarchical clustering of gene expression data from lung cancer cell lines could further verify the association of high <i>LINC00261</i>/<i>FOXA2</i> expression to an epithelial gene signature. Furthermore, higher expression of the <i>LINC00261</i>/<i>FOXA2</i> locus was associated with lung cancer cell lines with lower migratory capacity. All these data establish <i>LINC00261</i> and <i>FOXA2</i> as an epithelial-specific marker pair, downregulated during EMT and lung cancer progression, and associated with lower cell migration potential in lung cancer cells.