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

  1. Feichtenschlager, Valentin
  2. Chen, Linan
  3. Zheng, Yixuan James
  4. Ho, Wilson
  5. Sanlorenzo, Martina
  6. Vujic, Igor
  7. Fewings, Eleanor
  8. Lee, Albert
  9. Chen, Christopher
  10. Callanan, Ciara
  11. Lin, Kevin
  12. Qu, Tiange
  13. Hohlova, Dasha
  14. Vujic, Marin
  15. Hwang, Yeonjoo
  16. Lai, Kevin
  17. Chen, Stephanie
  18. Nguyen, Thuan
  19. Muñoz, Denise P
  20. Kohwi, Yoshinori
  21. Posch, Christian
  22. Daud, Adil
  23. Rappersberger, Klemens
  24. Kohwi-Shigematsu, Terumi
  25. Coppé, Jean-Philippe
  26. Ortiz-Urda, Susana

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1000 Titel
  • The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cancer cells’ survival in NRAS/MAPK-driven melanoma
1000 Autor/in
  1. Feichtenschlager, Valentin |
  2. Chen, Linan |
  3. Zheng, Yixuan James |
  4. Ho, Wilson |
  5. Sanlorenzo, Martina |
  6. Vujic, Igor |
  7. Fewings, Eleanor |
  8. Lee, Albert |
  9. Chen, Christopher |
  10. Callanan, Ciara |
  11. Lin, Kevin |
  12. Qu, Tiange |
  13. Hohlova, Dasha |
  14. Vujic, Marin |
  15. Hwang, Yeonjoo |
  16. Lai, Kevin |
  17. Chen, Stephanie |
  18. Nguyen, Thuan |
  19. Muñoz, Denise P |
  20. Kohwi, Yoshinori |
  21. Posch, Christian |
  22. Daud, Adil |
  23. Rappersberger, Klemens |
  24. Kohwi-Shigematsu, Terumi |
  25. Coppé, Jean-Philippe |
  26. Ortiz-Urda, Susana |
1000 Verlag BioMed Central
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-02-22
1000 Erschienen in
1000 Quellenangabe
  • 23(1):40
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s12943-024-01955-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10882889/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>AC004540.4</jats:italic>) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named <jats:italic>T-RECS</jats:italic>. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target <jats:italic>T-RECS</jats:italic>. <jats:italic>T-RECS</jats:italic> ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with <jats:italic>T-RECS</jats:italic> 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 <jats:italic>T-RECS</jats:italic> ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated <jats:italic>T-RECS</jats:italic> inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.</jats:p>
1000 Sacherschließung
lokal Membrane Proteins/genetics [MeSH]
lokal Cell Line, Tumor [MeSH]
lokal HT-KAM
lokal Melanoma
lokal Humans [MeSH]
lokal RNA, Long Noncoding/genetics [MeSH]
lokal Apoptosis
lokal Antisense oligonucleotides
lokal Animals [MeSH]
lokal GTP Phosphohydrolases/metabolism [MeSH]
lokal T-RECS
lokal MAPK-pathway
lokal lncRNA
lokal Oligonucleotides, Antisense/therapeutic use [MeSH]
lokal Mice [MeSH]
lokal Melanoma/pathology [MeSH]
lokal Research
lokal hnRNPA2/B1
lokal Apoptosis/genetics [MeSH]
lokal Oligonucleotides, Antisense/genetics [MeSH]
lokal GTP Phosphohydrolases/genetics [MeSH]
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. Verein zur Förderung der Dermatologischen Forschung |
  2. Impact Melanoma |
  3. Outrun the Sun, Inc. 2019 National Melanoma Research Scholar Award |
  4. HDFCCC Laboratory for Cell Analysis Shared Resource Facility |
1000 Fördernummer
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  4. -
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1000 Dateien
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  1. 1000 joinedFunding-child
    1000 Förderer Verein zur Förderung der Dermatologischen Forschung |
    1000 Förderprogramm -
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Impact Melanoma |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Outrun the Sun, Inc. 2019 National Melanoma Research Scholar Award |
    1000 Förderprogramm -
    1000 Fördernummer -
  4. 1000 joinedFunding-child
    1000 Förderer HDFCCC Laboratory for Cell Analysis Shared Resource Facility |
    1000 Förderprogramm -
    1000 Fördernummer -
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1000 Erstellt am 2025-07-05T13:54:07.732+0200
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1000 Zuletzt bearbeitet 2025-08-15T21:03:48.516+0200
1000 Objekt bearb. Fri Aug 15 21:03:48 CEST 2025
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