CBX2 shapes chromatin accessibility promoting AML via p38 MAPK signaling pathway.
CBX2
Cancer
Chromatin readers
Epigenetics
Leukemia
PcG
Journal
Molecular cancer
ISSN: 1476-4598
Titre abrégé: Mol Cancer
Pays: England
ID NLM: 101147698
Informations de publication
Date de publication:
09 06 2022
09 06 2022
Historique:
received:
19
01
2022
accepted:
31
05
2022
entrez:
10
6
2022
pubmed:
11
6
2022
medline:
14
6
2022
Statut:
epublish
Résumé
The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered chromatin readers involved in leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that the PRC1 complex member CBX2 is overexpressed in solid tumors and promotes cancer cell survival. However, its role in leukemia is still unclear. We exploited reverse genetic approaches to investigate the role of CBX2 in human leukemic cell lines and ex vivo samples. We also analyzed phenotypic effects following CBX2 silencing using cellular and molecular assays and related functional mechanisms by ATAC-seq and RNA-seq. We then performed bioinformatic analysis of ChIP-seq data to explore the influence of histone modifications in CBX2-mediated open chromatin sites. Lastly, we used molecular assays to determine the contribution of CBX2-regulated pathways to leukemic phenotype. We found CBX2 overexpressed in leukemia both in vitro and ex vivo samples compared to CD34 Our results identify CBX2 as a crucial player in leukemia progression and highlight a potential druggable CBX2-p38 MAPK network in AML.
Sections du résumé
BACKGROUND
The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered chromatin readers involved in leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that the PRC1 complex member CBX2 is overexpressed in solid tumors and promotes cancer cell survival. However, its role in leukemia is still unclear.
METHODS
We exploited reverse genetic approaches to investigate the role of CBX2 in human leukemic cell lines and ex vivo samples. We also analyzed phenotypic effects following CBX2 silencing using cellular and molecular assays and related functional mechanisms by ATAC-seq and RNA-seq. We then performed bioinformatic analysis of ChIP-seq data to explore the influence of histone modifications in CBX2-mediated open chromatin sites. Lastly, we used molecular assays to determine the contribution of CBX2-regulated pathways to leukemic phenotype.
RESULTS
We found CBX2 overexpressed in leukemia both in vitro and ex vivo samples compared to CD34
CONCLUSIONS
Our results identify CBX2 as a crucial player in leukemia progression and highlight a potential druggable CBX2-p38 MAPK network in AML.
Identifiants
pubmed: 35681235
doi: 10.1186/s12943-022-01603-y
pii: 10.1186/s12943-022-01603-y
pmc: PMC9178829
doi:
Substances chimiques
CBX2 protein, human
0
Chromatin
0
Polycomb Repressive Complex 1
EC 2.3.2.27
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
125Informations de copyright
© 2022. The Author(s).
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