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Long non-coding RNA triplex-dependent regulation of melanoma gene networks
Kushani Shah1,2,3, Eleni Anastasakou1,2,3, Leinal Sejour3,4
1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.
SLNCR, a long non-coding RNA, drives melanoma progression by forming RNA•DNA:DNA triplexes with key gene promoters. Blocking these triplexes inhibits melanoma cell migration, highlighting a novel therapeutic target.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Long non-coding RNAs (lncRNAs) play critical roles in gene regulation.
- SLNCR is implicated in melanoma formation and gene expression regulation through transcription factor interactions.
Purpose of the Study:
- To investigate the mechanism by which SLNCR promotes melanoma progression.
- To determine if SLNCR forms RNA•DNA triplexes and if these interactions are functional.
Main Methods:
- RNA sequencing
- Triplex Domain Finder tool analysis
- Functional assays using A375 melanoma cells
- Ex vivo migration assays with inhibitory oligonucleotides
Main Results:
- SLNCR contains four triplex-forming regions (TFRs) homologous to other lncRNAs.
- SLNCR TFRs form RNA•DNA:DNA triplexes with target sites in promoters of genes regulating melanoma migration and invasion.
- Overexpression of full-length SLNCR promotes melanoma cell proliferation, migration, and invasion.
- Deletion of TFRs reverses SLNCR's transcriptomic signature and impairs its function.
- Inhibitory oligos blocking SLNCR•DNA:DNA triplex formation reversed SLNCR-mediated migration.
Conclusions:
- SLNCR promotes melanoma progression through the formation of RNA•DNA:DNA triplexes.
- These triplexes target key genes involved in melanoma migration and invasion networks.
- Targeting SLNCR•DNA:DNA triplex formation represents a potential therapeutic strategy for melanoma.
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