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

Li-Nan Chen,

Yixuan James Zheng

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Дек. 1, 2023

Abstract 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 discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified nuclear-enriched lncRNA ( AC004540.4 ) that is upregulated NRAS/MAPK-dependent melanoma, named T-RECS . Considering potential innovative treatment strategies, designed antisense oligonucleotides (ASOs) target ASOs reduced the growth cells induced apoptotic cell death, while having minimal impacton normal primary melanocytes. Mechanistically, with downregulated activity pro-survival kinases protein stability hnRNPA2/B1, pro-oncogenic regulator MAPK signaling. patient- line- derived tumor xenograft mouse models, demonstrated systemic significantly suppressed tumors, no noticeable toxicity. ASO-mediated inhibition represents promising RNA-targeting improve outcome pathway-activated melanoma.

Язык: Английский

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

Li-Nan Chen,

Yixuan James Zheng

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Дек. 1, 2023

Abstract 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 discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified nuclear-enriched lncRNA ( AC004540.4 ) that is upregulated NRAS/MAPK-dependent melanoma, named T-RECS . Considering potential innovative treatment strategies, designed antisense oligonucleotides (ASOs) target ASOs reduced the growth cells induced apoptotic cell death, while having minimal impacton normal primary melanocytes. Mechanistically, with downregulated activity pro-survival kinases protein stability hnRNPA2/B1, pro-oncogenic regulator MAPK signaling. patient- line- derived tumor xenograft mouse models, demonstrated systemic significantly suppressed tumors, no noticeable toxicity. ASO-mediated inhibition represents promising RNA-targeting improve outcome pathway-activated melanoma.

Язык: Английский

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