Abstract
Metastatic melanoma of the skin has a high mortality despite the recent introduction of targeted therapy and immunotherapy. Long non-coding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides in length that lack protein-coding potential. There is growing evidence that lncRNAs play an important role in gene regulation, including oncogenesis. We present 13 lncRNA genes involved in the pathogenesis of cutaneous melanoma through a variety of pathways and molecular interactions. Some of these lncRNAs are possible biomarkers or therapeutic targets for malignant melanoma.
Highlights
2% of the human genome sequence is translated into proteins.[1]
We present 13 Long non-coding RNAs (lncRNAs) genes involved in the pathogenesis of cutaneous melanoma through a variety of pathways and molecular interactions
The lncRNAs reported to be involved in the pathogenesis of cutaneous melanoma exert their function through different pathways and they interact with different molecular targets
Summary
The functional evaluation of lncRNAs often relies on suppressing the activity of lncRNA (knockdown) and observing the resulting molecular phenotypes. LncRNAs can repress gene expression through recruitment of the polycomb repressive complex 2 (PRC2) towards specific loci in the genome, resulting in tri-methylation of H3K27, marking transcriptionally silent chromatin. This mechanism was observed for HOTAIR, a lncRNA transcribed from the HOXC locus that interacts with PRC2.[18] Alternatively, lncRNAs can activate gene expression. This can occur through recruitment of the WDR5/MLL complex, resulting in tri-methylation of H3K4 [19] or through the recruitment of the Mediator complex, resulting in phosphorylation of H3S10 [20]. Apart from a functional classification, lncRNAs are often categorized on the basis of their genomic location and orientation compared to protein-coding genes (eg, sense, antisense, intronic of intergenic).[21, 23, 24]
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