Long non-coding RNA triplex-dependent regulation of melanoma gene networks

SLNCR is a long non-coding RNA that promotes melanoma formation. Previously, we have shown that SLNCR regulates gene expression and melanomagenesis via interacting with different transcription factors. Here we show that SLNCR is associated with several genomic sites that contain RNA: DNA triplex target sites (TTSs). The primary sequence of SLNCR contains 4 triplex forming regions (TFRs), which are homologous to the TFRs of MEG3, HOTAIR, and PARTICLE lncRNAs. Full-length SLNCR overexpression promotes proliferation, migration, and invasion of melanoma cells and induces characteristic gene expression changes that are reversed by deletions of TFS-1, -2, -4, or -5. These triplex-dependent genes are enriched in pathways involved in cell cycle regulation and cell migration. We directly demonstrate that SLNCR TFRs can form RNA•DNA-DNA triplexes with the TTSs in promoters of genes, suggesting network level gene regulation. Finally, inhibitory oligos that block SLNCR•DNA-DNA triplex formation reversed the effect of SLNCR-mediated migration and proliferation ex vivo demonstrating that triplex formation might play a role in driving melanoma progression.