Plastic and reconstructive surgery. Global open · 2026
Mendelian Randomization Unveils Poly(ADP-ribose) Polymerase 1 as Causal Plasma Protein Target in Melanoma, Integrated Multi-omics.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lu Feng, Luan Wenkang, Jiang Hanyi, Ma Shaojun, Ruan Hongru
Аннотация
BACKGROUND: The molecular regulators driving melanoma pathogenesis remain incompletely defined. Although plasma proteins show associations with melanoma, their causal relationships are unclear.
METHODS: We performed Mendelian randomization (MR) using proteomic data from the UK Biobank Pharma Proteomics Project and deCODE genetics to identify plasma proteins causally linked to melanoma. Colocalization, summary data-based MR, heterogeneity in dependent instruments, and MR-phenome-wide association study analyses identified druggable targets. Transcriptome profiling of melanoma tissues and single-cell functional validation assessed the target roles.
RESULTS: Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) was established as a causal risk factor and druggable target for melanoma. Elevated PARP1 expression in melanoma tissues correlated with poor patient survival. Functional analyses revealed that PARP1 coordinates protumorigenic functions with cell-specific roles.
CONCLUSIONS: In conclusion, our results demonstrate that PARP1 is a key driver of melanoma pathogenesis and represents a potential specific molecular target for therapeutic intervention.
METHODS: We performed Mendelian randomization (MR) using proteomic data from the UK Biobank Pharma Proteomics Project and deCODE genetics to identify plasma proteins causally linked to melanoma. Colocalization, summary data-based MR, heterogeneity in dependent instruments, and MR-phenome-wide association study analyses identified druggable targets. Transcriptome profiling of melanoma tissues and single-cell functional validation assessed the target roles.
RESULTS: Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) was established as a causal risk factor and druggable target for melanoma. Elevated PARP1 expression in melanoma tissues correlated with poor patient survival. Functional analyses revealed that PARP1 coordinates protumorigenic functions with cell-specific roles.
CONCLUSIONS: In conclusion, our results demonstrate that PARP1 is a key driver of melanoma pathogenesis and represents a potential specific molecular target for therapeutic intervention.