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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE302468 | GEO | 2026/05/26

REPOSITORIES: GEO

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Project description:Schmitz2014 - RNA triplex formation The model is parameterized using the parameters for gene CCDC3 from Supplementary Table S1. The two miRNAs which form the triplex together with CCDC3 are miR-551b and miR-138. This model is described in the article: Cooperative gene regulation by microRNA pairs and their identification using a computational workflow. Schmitz U, Lai X, Winter F, Wolkenhauer O, Vera J, Gupta SK. Nucleic Acids Res. 2014 Jul; 42(12): 7539-7552 Abstract: MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergize and which genes are target of cooperative miRNA regulation. In this paper, we present a computational workflow for the prediction and analysis of cooperating miRNAs and their mutual target genes, which we refer to as RNA triplexes. The workflow integrates methods of miRNA target prediction; triplex structure analysis; molecular dynamics simulations and mathematical modeling for a reliable prediction of functional RNA triplexes and target repression efficiency. In a case study we analyzed the human genome and identified several thousand targets of cooperative gene regulation. Our results suggest that miRNA cooperativity is a frequent mechanism for an enhanced target repression by pairs of miRNAs facilitating distinctive and fine-tuned target gene expression patterns. Human RNA triplexes predicted and characterized in this study are organized in a web resource at www.sbi.uni-rostock.de/triplexrna/. This model is hosted on BioModels Database and identified by: BIOMD0000000530. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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

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