Department of Genetics at Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil.
Sci Rep. 2019 Aug 5;9(1):11350. 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.
黑色素瘤是最致命的皮肤癌形式，目前对于长链非编码 RNA（lncRNA）表达失调在这种癌症进展中的影响知之甚少。在这项研究中，我们探索了 RNA-Seq 数据，以寻找与黑色素瘤进展相关的 lncRNA。我们发现黑色素细胞、原发性和转移性黑色素瘤细胞之间存在明显的 lncRNA 基因表达模式。此外，我们观察到 lncRNA ZEB1-AS1（ZEB1 反义 RNA 1）在黑色素瘤细胞系中的上调。来自癌症基因组图谱（TCGA）的数据分析证实，转移性黑色素瘤中 ZEB1-AS1 的表达更高，并且与 BRAF（B-Raf 原癌基因，丝氨酸/苏氨酸激酶）基因和 RAS 家族基因的热点突变相关。此外，在原发性和转移性黑色素瘤中还验证了 ZEB1-AS1 和 ZEB1（锌指 E 盒结合同源盒 1）基因表达之间的正相关。使用提示侵袭性或增殖表型的基因表达特征，我们发现 ZEB1-AS1 上调与侵袭性转录谱之间存在关联。相关基因的富集分析表明，ZEB1-AS1 与癌症基因和途径相关。我们认为，lncRNA ZEB1-AS1 可能通过激活 ZEB1 基因表达来发挥作用，从而影响黑色素瘤的侵袭性和表型转换，这是一种上皮-间充质转化（EMT）样过程，其中 ZEB1 基因起着至关重要的作用。
