The positionally conserved lncRNA DANCR is an essential regulator of zebrafish development and a human melanoma oncogene

Long non-coding RNAs (lncRNAs) can regulate gene expression. Some are essential for organismal development and physiology and can contribute to diseases including cancer. Whilst most lncRNAs exhibit little sequence similarity, conservation of lncRNA transcription relative to neighbouring protein-coding genes suggests potential functional significance. Most positionally equivalent lncRNAs are uncharacterized and it remains unclear whether they exert similar roles in distant species. Here, we identified syntenic melanoma-associated lncRNAs predicted to be components of the MITF gene regulatory network in human melanoma, with positionally equivalent transcripts in zebrafish. We prioritizedDifferentiation Antagonizing Non-Protein Coding RNA(DANCR), a cancer-associated lncRNA critical for maintaining somatic progenitor cells in human models, for functional investigation.Dancris a multi-exonic, cytoplasmically-enriched lncRNA transcribed from syntenic regions in the human and zebrafish genomes. MITF and c-MYC, key melanoma transcription factors, regulate humanDANCRexpression and melanoma patients with highDANCRdisplay significantly decreased survival.DANCRis a melanoma oncogene that controls cancer-associated gene expression networks and promotes human melanoma cell proliferation and migration. Zebrafishdancris dynamically expressed across multiple different cell types in the developing embryo, regulates genes involved in cell death, and is essential for embryonic development. Our work suggests that cancer-critical lncRNAs such asDANCR, expressed from similar regions in vertebrate genomes, may regulate related genes and processes involved in both embryonic development and tumorigenesis across species.