RNA splicing dysregulation and the hallmarks of cancer.


Journal

Nature reviews. Cancer
ISSN: 1474-1768
Titre abrégé: Nat Rev Cancer
Pays: England
ID NLM: 101124168

Informations de publication

Date de publication:
03 2023
Historique:
accepted: 28 11 2022
pubmed: 11 1 2023
medline: 3 3 2023
entrez: 10 1 2023
Statut: ppublish

Résumé

Dysregulated RNA splicing is a molecular feature that characterizes almost all tumour types. Cancer-associated splicing alterations arise from both recurrent mutations and altered expression of trans-acting factors governing splicing catalysis and regulation. Cancer-associated splicing dysregulation can promote tumorigenesis via diverse mechanisms, contributing to increased cell proliferation, decreased apoptosis, enhanced migration and metastatic potential, resistance to chemotherapy and evasion of immune surveillance. Recent studies have identified specific cancer-associated isoforms that play critical roles in cancer cell transformation and growth and demonstrated the therapeutic benefits of correcting or otherwise antagonizing such cancer-associated mRNA isoforms. Clinical-grade small molecules that modulate or inhibit RNA splicing have similarly been developed as promising anticancer therapeutics. Here, we review splicing alterations characteristic of cancer cell transcriptomes, dysregulated splicing's contributions to tumour initiation and progression, and existing and emerging approaches for targeting splicing for cancer therapy. Finally, we discuss the outstanding questions and challenges that must be addressed to translate these findings into the clinic.

Identifiants

pubmed: 36627445
doi: 10.1038/s41568-022-00541-7
pii: 10.1038/s41568-022-00541-7
pmc: PMC10132032
mid: NIHMS1888944
doi:

Substances chimiques

Protein Isoforms 0

Types de publication

Journal Article Review Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

135-155

Subventions

Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151651
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA251138
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM138541
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128239
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248317
Pays : United States

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Robert K Bradley (RK)

Computational Biology Program, Public Health Sciences Division and Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. rbradley@fredhutch.org.

Olga Anczuków (O)

The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. olga.anczukow@jax.org.
Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, USA. olga.anczukow@jax.org.

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