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

• Published in: Scientific reports Vol. 9; no. 1; pp. 11350 - 11
• Main Authors: Siena, Ádamo Davi Diógenes, Plaça, Jéssica Rodrigues, Araújo, Luiza Ferreira, de Barros, Isabela Ichihara, Peronni, Kamila, Molfetta, Greice, de Biagi, Carlos Alberto Oliveira, Espreafico, Enilza Maria, Sousa, Josane Freitas, Silva, Wilson Araújo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-08-2019; Nature Publishing Group
• Subjects: 38/39; 38/47; 38/90; 38/91; 631/208/199; 631/208/212/2019; 631/337/384/2568; 631/67/1813/1634; Antisense RNA; Cell Line, Tumor; Cell Proliferation - genetics; Epithelial-Mesenchymal Transition - genetics; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Genomes; Homeobox; Humanities and Social Sciences; Humans; Invasiveness; Kinases; Male; Melanocytes; Melanoma; Melanoma - genetics; Melanoma - pathology; Mesenchyme; Metastases; Metastasis; multidisciplinary; Mutation hot spots; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Metastasis; Phenotypes; Protein-serine/threonine kinase; Raf protein; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Science; Science (multidisciplinary); Skin cancer; Transcription; Transcriptome - genetics; Zinc finger proteins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-47363-6

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.