The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma

Mol Cancer. 2024 Feb 22;23(1):40. doi: 10.1186/s12943-024-01955-7.


Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.

Keywords: Antisense oligonucleotides; Apoptosis; HT-KAM; MAPK-pathway; Melanoma; T-RECS; hnRNPA2/B1; lncRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Melanoma* / pathology
  • Membrane Proteins / genetics
  • Mice
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / therapeutic use
  • RNA, Long Noncoding* / genetics


  • RNA, Long Noncoding
  • Oligonucleotides, Antisense
  • NRAS protein, human
  • Membrane Proteins
  • GTP Phosphohydrolases