Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes.
DNA replication
E2F2
E2F8
Musashi1
cell cycle
cell division
glioblastoma
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
24 Mar 2021
24 Mar 2021
Historique:
received:
06
02
2021
revised:
17
03
2021
accepted:
21
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
4
4
2021
Statut:
epublish
Résumé
RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in their levels are often observed in tumors with numerous oncogenic RBPs identified in recent years. Musashi1 (Msi1) is an RBP and stem cell gene that controls the balance between self-renewal and differentiation. High Msi1 levels have been observed in multiple tumors including glioblastoma and are often associated with poor patient outcomes and tumor growth. A comprehensive genomic analysis identified a network of cell cycle/division and DNA replication genes and established these processes as Msi1's core regulatory functions in glioblastoma. Msi1 controls this gene network via two mechanisms: direct interaction and indirect regulation mediated by the transcription factors E2F2 and E2F8. Moreover, glioblastoma lines with Msi1 knockout (KO) displayed increased sensitivity to cell cycle and DNA replication inhibitors. Our results suggest that a drug combination strategy (Msi1 + cell cycle/DNA replication inhibitors) could be a viable route to treat glioblastoma.
Identifiants
pubmed: 33804958
pii: cancers13071494
doi: 10.3390/cancers13071494
pmc: PMC8036803
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIH HHS
ID : 1 R21 NS113344-01A1
Pays : United States
Organisme : NIH HHS
ID : S10 OD021805
Pays : United States
Organisme : NIH HHS
ID : 2R01 HG006015
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA054174
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS113344
Pays : United States
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