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The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.
In: Molecular Cancer, Jg. 23 (2024-02-22), Heft 1, S. 1-21
Online
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
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Titel: |
The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.
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Autor/in / Beteiligte Person: | Feichtenschlager, Valentin ; Chen, Linan ; Zheng, Yixuan James ; Ho, Wilson ; Sanlorenzo, Martina ; Vujic, Igor ; Fewings, Eleanor ; Lee, Albert ; Chen, Christopher ; Callanan, Ciara ; Lin, Kevin ; Qu, Tiange ; Hohlova, Dasha ; Vujic, Marin ; Hwang, Yeonjoo ; Lai, Kevin ; Chen, Stephanie ; Nguyen, Thuan ; Muñoz, Denise P ; Kohwi, Yoshinori |
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Zeitschrift: | Molecular Cancer, Jg. 23 (2024-02-22), Heft 1, S. 1-21 |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 1476-4598 (print) |
DOI: | 10.1186/s12943-024-01955-7 |
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