Comprehensive microRNA analysis across genome-edited colorectal cancer organoid models reveals miR-24 as a candidate regulator of cell survival.
CRISPR/Cas9
Colorectal cancer
MicroRNA
Organoid
Precision medicine
Tumor heterogeneity
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
received:
26
07
2022
accepted:
17
11
2022
entrez:
2
12
2022
pubmed:
3
12
2022
medline:
6
12
2022
Statut:
epublish
Résumé
Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify 12 different modules of microRNA expression patterns across different combinations of mutations common in CRC. We also show that miR-24-3p is aberrantly upregulated in genetically-modified mouse enteroids irrespective of mutational context. Furthermore, we identify an enrichment of miR-24-3p predicted targets in downregulated gene lists from various mutational contexts compared to WT. In follow-up experiments, we demonstrate that miR-24-3p promotes CRC cell survival in multiple cell contexts. Our novel characterization of genotype-specific patterns of miRNA expression offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.
Identifiants
pubmed: 36457077
doi: 10.1186/s12864-022-09018-1
pii: 10.1186/s12864-022-09018-1
pmc: PMC9716731
doi:
Substances chimiques
MicroRNAs
0
Mirn24 microRNA, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
792Subventions
Organisme : Cornell University
ID : Intercampus Seed Grant
Organisme : Cornell University
ID : Intercampus Seed Grant
Organisme : Cornell University
ID : Intercampus Seed Grant
Informations de copyright
© 2022. The Author(s).
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