CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells.
CRISPR/Cas9
MYC
MYC target genes
high-throughput screen
transcription factor
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
28
04
2023
received:
10
02
2023
accepted:
21
07
2023
medline:
3
11
2023
pubmed:
31
7
2023
entrez:
31
7
2023
Statut:
ppublish
Résumé
The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines-K562, ST486, HepG2, and MCF7-which revealed several essential E-boxes and genes. Among them, we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression, and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.
Identifiants
pubmed: 37519063
doi: 10.1002/1878-0261.13493
pmc: PMC10620128
doi:
Substances chimiques
Proto-Oncogene Proteins c-myc
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2295-2313Subventions
Organisme : H2020 Spreading Excellence and Widening Participation
ID : 952304
Organisme : Narodowe Centrum Nauki
ID : 2016/23/D/NZ1/01611
Organisme : Narodowe Centrum Nauki
ID : 2017/26/D/NZ1/01234
Informations de copyright
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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