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Updated: Jul 8, 2025

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The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in

Valentin Feichtenschlager1, Linan Chen1, Yixuan James Zheng1

  • 1University of California San Francisco.

Research Square
|December 11, 2023
PubMed

Insights

Targeting the T-RECS long non-coding RNA with antisense oligonucleotides (ASOs) effectively inhibits NRAS-mutated melanoma growth. This RNA-targeting strategy shows promise for treating MAPK pathway-activated melanoma with minimal toxicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • RNA Therapeutics

Background:

  • NRAS-mutated melanoma presents a significant therapeutic challenge.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators in cancer development.
  • Identifying novel therapeutic targets is crucial for improving patient outcomes in melanoma.

Approach:

  • Utilized a combined experimental and computational approach to identify novel lncRNAs in melanoma.
  • Discovered and validated a nuclear-enriched lncRNA, T-RECS (AC004540.4), upregulated in NRAS/MAPK-dependent melanoma.
  • Designed and tested antisense oligonucleotides (ASOs) targeting T-RECS in preclinical melanoma models.

Key Points:

  • T-RECS ASOs demonstrated significant melanoma cell growth inhibition and induced apoptosis.
  • T-RECS ASOs downregulated pro-survival kinase activity and hnRNPA2/B1 protein stability.
  • Systemic ASO treatment targeting T-RECS suppressed tumor growth in xenograft models with no observed toxicity.

Conclusions:

  • ASO-mediated inhibition of T-RECS is a potential therapeutic strategy for NRAS-mutated melanoma.
  • This RNA-targeting approach offers a promising avenue for treating MAPK pathway-activated melanoma.
  • T-RECS ASOs represent a novel therapeutic modality with a favorable safety profile in preclinical studies.
Keywords:
ASOAntisense OligonucleotidesMAPK-pathwayNRAST-RECSlncRNAmelanoma

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