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Melanoma is the deadliest form of skin cancer, and little is known about the impact of deregulated expression of long noncoding RNAs (lncRNAs) in the progression of this cancer. In this study, we explored RNA-Seq data to search for lncRNAs associated with melanoma progression. We found distinct lncRNA gene expression patterns across melanocytes, primary and metastatic melanoma cells. Also, we observed upregulation of the lncRNA  ZEB1-AS1  (ZEB1 antisense RNA 1) in melanoma cell lines. Data analysis from The Cancer Genome Atlas (TCGA) confirmed higher  ZEB1-AS1  expression in metastatic melanoma and its association with hotspot mutations in  BRAF  (B-Raf proto-oncogene, serine/threonine kinase) gene and  RAS  family genes. In addition, a positive correlation between  ZEB1-AS1  and  ZEB1  (zinc finger E-box binding homeobox 1) gene expression was verified in primary and metastatic melanomas. Using gene expression signatures indicative of invasive or proliferative phenotypes, we found an association between  ZEB1-AS1  upregulation and a transcriptional profile for invasiveness. Enrichment analysis of correlated genes demonstrated cancer genes and pathways associated with  ZEB1-AS1 . We suggest that the lncRNA  ZEB1-AS1  could function by activating  ZEB1  gene expression, thereby influencing invasiveness and phenotype switching in melanoma, an epithelial-to-mesenchymal transition (EMT)-like process, which the  ZEB1  gene has an essential role.

Whole transcriptome analysis reveals correlation of long noncoding RNA ZEB1-AS1 with invasive profile in melanoma