Exploring RNA biology in pseudomyxoma peritonei uncovers splicing dysregulation as a novel, targetable molecular vulnerability DOI Creative Commons
María Trinidad Moreno-Montilla, Sergio Pedraza‐Arévalo, Ana Martínez-López

et al.

Cancer Gene Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Pseudomyxoma peritonei (PMP) is a rare neoplasm coursing with uncontrollable mucus accumulation, high relapse rate. RNA biology processes have emerged as new players in cancer development and progression, nevertheless their role PMP remains unknown. In this study, we aimed to examine RNA-regulatory machineries potential contribution disease progression. We analyzed 62 splicing-related genes, 27 exosome 21 nonsense-mediated decay cohort of 29 patients using microfluidic array, comparing tumor control/reference tissues, together external RNA-seq proteomic data. Our results revealed profound dysregulation key components, which correlated relevant clinical parameters enabled distinguish between control tissues. vitro splicing inhibition Pladienolide-B, well the modulation specific factors, reduced aggressiveness parameters, enhanced effect clinically used drugs, strong correlation dysregulated genes cancer-related genes. This also affected mucin secretion variants production. Collectively, our findings provide first evidence for pivotal PMP, implying that these targetable mechanisms may be functionally altered play disease. Hence, thorough understanding its could aid discovery actionable vulnerabilities

Language: Английский

Exploring RNA biology in pseudomyxoma peritonei uncovers splicing dysregulation as a novel, targetable molecular vulnerability DOI Creative Commons
María Trinidad Moreno-Montilla, Sergio Pedraza‐Arévalo, Ana Martínez-López

et al.

Cancer Gene Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Pseudomyxoma peritonei (PMP) is a rare neoplasm coursing with uncontrollable mucus accumulation, high relapse rate. RNA biology processes have emerged as new players in cancer development and progression, nevertheless their role PMP remains unknown. In this study, we aimed to examine RNA-regulatory machineries potential contribution disease progression. We analyzed 62 splicing-related genes, 27 exosome 21 nonsense-mediated decay cohort of 29 patients using microfluidic array, comparing tumor control/reference tissues, together external RNA-seq proteomic data. Our results revealed profound dysregulation key components, which correlated relevant clinical parameters enabled distinguish between control tissues. vitro splicing inhibition Pladienolide-B, well the modulation specific factors, reduced aggressiveness parameters, enhanced effect clinically used drugs, strong correlation dysregulated genes cancer-related genes. This also affected mucin secretion variants production. Collectively, our findings provide first evidence for pivotal PMP, implying that these targetable mechanisms may be functionally altered play disease. Hence, thorough understanding its could aid discovery actionable vulnerabilities

Language: Английский

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