Low expression of the dynamic network markers FOS/JUN in pre-deteriorated epithelial cells is associated with the progression of colorectal adenoma to carcinoma.
J Transl Med
; 21(1): 45, 2023 01 25.
Article
en En
| MEDLINE
| ID: mdl-36698183
ABSTRACT
BACKGROUND:
Deterioration of normal intestinal epithelial cells is crucial for colorectal tumorigenesis. However, the process of epithelial cell deterioration and molecular networks that contribute to this process remain unclear.METHODS:
Single-cell data and clinical information were downloaded from the Gene Expression Omnibus (GEO) database. We used the recently proposed dynamic network biomarker (DNB) method to identify the critical stage of epithelial cell deterioration. Data analysis and visualization were performed using R and Cytoscape software. In addition, Single-Cell rEgulatory Network Inference and Clustering (SCENIC) analysis was used to identify potential transcription factors, and CellChat analysis was conducted to evaluate possible interactions among cell populations. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set variation analysis (GSVA) analyses were also performed.RESULTS:
The trajectory of epithelial cell deterioration in adenoma to carcinoma progression was delineated, and the subpopulation of pre-deteriorated epithelial cells during colorectal cancer (CRC) initialization was identified at the single-cell level. Additionally, FOS/JUN were identified as biomarkers for pre-deteriorated epithelial cell subpopulations in CRC. Notably, FOS/JUN triggered low expression of P53-regulated downstream pro-apoptotic genes and high expression of anti-apoptotic genes through suppression of P53 expression, which in turn inhibited P53-induced apoptosis. Furthermore, malignant epithelial cells contributed to the progression of pre-deteriorated epithelial cells through the GDF signaling pathway.CONCLUSIONS:
We demonstrated the trajectory of epithelial cell deterioration and used DNB to characterize pre-deteriorated epithelial cells at the single-cell level. The expression of DNB-neighboring genes and cellular communication were triggered by DNB genes, which may be involved in epithelial cell deterioration. The DNB genes FOS/JUN provide new insights into early intervention in CRC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma
/
Neoplasias Colorrectales
/
Adenoma
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Transl Med
Año:
2023
Tipo del documento:
Article
País de afiliación:
China