Sustained Cancer-relevant Alternative RNA Splicing Events Driven by PRMT5 in High-risk Neuroblastoma

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2024 Jul 18

PMID 39021294

Authors

Laurel Tabe Bate-Eya

Gulsah Albayrak

Simon Mark Carr

Amit Shrestha

Alexander Kanapin

Anastasia Samsonova

Nicholas Barrie La Thangue

Affiliations

Soon will be listed here.

Abstract

Protein arginine methyltransferase 5 (PRMT5) is over-expressed in a wide variety of cancers and is implicated as having a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1. We investigated the relevance of PRMT5 and E2F1 in neuroblastoma (NB) and found that elevated expression of PRMT5 and E2F1 occurs in poor prognosis high-risk disease and correlates with an amplified Myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) gene. Our results show that MYCN drives the expression of splicing factor genes that, together with PRMT5 and E2F1, lead to a deregulated alternative RNA splicing programme that impedes apoptosis. Pharmacological inhibition of PRMT5 or inactivation of E2F1 restores normal splicing and renders NB cells sensitive to apoptosis. Our findings suggest that a sustained cancer-relevant alternative RNA splicing programme desensitises NB cells to apoptosis, and identify PRMT5 as a potential therapeutic target for high-risk disease.

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