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

Abstract

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.

Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression

“…Transcriptome analysis can identify both coding and non-coding RNA, quantifying gene expression heterogeneity in cells, tissues, organs and even in the whole organism (50). Transcriptome analysis is important to investigate various processes (51) and it has been widely used to identify key factors in the progression of multiple diseases (27,52-53). Kim et al (52), using transcriptome analysis, identified Tensin 4 as a key effector of cetuximab and a regulator of the oncogenic activity of KRAS-mutant colorectal cancer cell lines.…”

“…Yang et al (27) reported the transcriptome profiling of brain myeloid cells, and identified an upregulation of integrin subunit α L, triggering receptor expressed on myeloid cells 1 and secreted phosphoprotein 1 in Western diet-induced obesity. Siena et al (53) performed a whole transcriptome analysis in melanoma and identified a correlation between the expression level of the long non-coding RNA ZEB1-AS1 with invasive ability of melanoma cells. These previous studies suggested that the transcriptome has become a reliable tool to identify key factors in the development and progression of various diseases (27,52,53).…”

“…Siena et al (53) performed a whole transcriptome analysis in melanoma and identified a correlation between the expression level of the long non-coding RNA ZEB1-AS1 with invasive ability of melanoma cells. These previous studies suggested that the transcriptome has become a reliable tool to identify key factors in the development and progression of various diseases (27,52,53). The present study aimed to investigate the mechanism underlying tacrolimus nephrotoxicity and to identify novel potential targets via transcriptomic and bioinformatics analyses.…”

The Functional Role of Long Non-Coding RNAs in Melanoma

“…ZEB1 antisense RNA 1 (ZEB1-AS1) is located in the opposite strand of gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1). Transcription of both ZEB1-AS1 and ZEB1 is positively correlated in primary melanoma cells, when compared to melanocytes, and in metastatic melanoma cells, when compared to primary melanoma cells [ 177 ]. Apart from upregulating ZEB1, ZEB1-AS1 is suggested to sponge miR-1224-5p, which has been identified as a tumor suppressor in malignant gliomas.…”

The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy

“…Data analysis from TCGA confirmed the increased expression of ZEB1-AS1 in metastatic melanoma and its association with hotspot mutations in BRAF and RAS family genes. Additionally, enrichment analysis correlated ZEB1-AS1 with the gene expression of zinc finger E-box binding homeobox 1 ( ZEB1 ), an essential EMT marker, suggesting a possible role in melanoma invasiveness and phenotype switching [ 73 ].…”