Involvement of oncomiRs miR-23, miR-24, and miR-27 in the regulation of alternative polyadenylation in glioblastoma via CFIm25 cleavage factor.
Alternative polyadenylation
CFIm25
Glioblastoma
miR-23
miR-24
miR-27
microRNA
oncomiR
Journal
Metabolic brain disease
ISSN: 1573-7365
Titre abrégé: Metab Brain Dis
Pays: United States
ID NLM: 8610370
Informations de publication
Date de publication:
27 Aug 2024
27 Aug 2024
Historique:
received:
21
07
2023
accepted:
08
07
2024
medline:
27
8
2024
pubmed:
27
8
2024
entrez:
27
8
2024
Statut:
aheadofprint
Résumé
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. The cleavage factor Im 25 (CFIm25), a crucial component of the CFIm complex, plays a key role in regulating the length of the mRNA 3'-UTR and has been implicated in various cancers, including GBM. This study sought to investigate the regulatory influence of specific microRNAs (miRNAs) on CFIm25 expression in GBM, a highly aggressive brain tumor. Bioinformatics analysis identified miRNA candidates targeting CFIm25 mRNA, and gene expression profiles from the NCBI database (GSE90603) were used for further analysis. Expression levels of CFIm25 and selected miRNAs were assessed using qRT-PCR in GBM clinical samples (n = 20) and non-malignant brain tissues (n = 5). Additionally, the MTT assay was performed to examine the effect of miRNA overexpression on U251 cell viability. Lentivectors expressing the identified miRNAs were employed to experimentally validate their regulatory role on CFIm25 in U251 cell lines, and Western blot analysis was conducted to determine CFIm25 protein levels. We observed significantly increased levels of miR-23, miR-24, and miR-27 expression, associated with a marked reduction in CFIm25 expression in GBM samples compared to non-malignant brain tissues. In particular, overexpression of miR-23, miR-24, and miR-27 in U251 cells resulted in CFIm25 downregulation at both the mRNA and protein levels, while their inhibition increased CFIm25 and reduced cell proliferation. These observations strongly implicate miR-23, miR-24, and miR-27 in regulating CFIm25 expression in GBM, emphasizing their potential as promising therapeutic targets for enhancing treatment responses in glioblastoma.
Identifiants
pubmed: 39190234
doi: 10.1007/s11011-024-01394-9
pii: 10.1007/s11011-024-01394-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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