| Summary: | Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of <i>ZFAS1</i> and its potential as a biomarker in HNSCC. Methods: The expression level of <i>ZFAS1</i> in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the <i>ZFAS1</i> expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5. Results: The expression of <i>ZFAS1</i> was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of <i>ZFAS1</i> in HNSCCs compared to normal tissue samples. The <i>ZFAS1</i> levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of <i>ZFAS1</i> presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with <i>ZFAS1</i>, as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of <i>ZFAS1</i>, we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between <i>ZFAS1</i> and its host gene, <i>ZNFX1</i>, was observed. The analysis of interactions indicated that <i>ZFAS1</i> has a binding sequence for <i>miR-150-5p</i>. The expression of <i>ZFAS1</i> and <i>miR-150-5p</i> is negatively correlated in HNSCC patients. <i>miR-150-5p</i> can regulate the 3′UTR of <i>EIF4E</i> mRNA. In the group of patients with high expression of <i>ZFAS1</i> and low expression of <i>miR-150-5p</i>, we detected an up-regulation of <i>EIF4E</i>. Conclusions: In HNSCC, <i>ZFAS1</i> displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients’ clinical outcomes. <i>ZFAS1</i> likely regulates the cell phenotype through <i>miR-150-5p</i> and its downstream targets. Following further validation, <i>ZFAS1</i> might prove a new and valuable biomarker.
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