PUBLICATION
Colorectal cancer progression to metastasis is associated with dynamic genome-wide biphasic 5-hydroxymethylcytosine accumulation
- Authors
- Murcott, B., Honig, F., Halliwell, D.O., Tian, Y., Robson, J.L., Manasterski, P., Pinnell, J., Dix-Peek, T., Uribe-Lewis, S., Ibrahim, A.E.K., Sero, J., Gurevich, D., Nikolaou, N., Murrell, A.
- ID
- ZDB-PUB-250417-13
- Date
- 2025
- Source
- BMC Biology 23: 100100 (Journal)
- Registered Authors
- Nikolaou, Nikolas
- Keywords
- 5-Hydroxymethylcytosine, Colorectal cancer progression to metastasis, Epigenetics, Ten-eleven-translocation (TET), Zebrafish assay
- MeSH Terms
-
- Disease Progression
- Cell Line, Tumor
- 5-Methylcytosine*/analogs & derivatives
- 5-Methylcytosine*/metabolism
- Dioxygenases
- DNA Methylation
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Proto-Oncogene Proteins/genetics
- Proto-Oncogene Proteins/metabolism
- Zebrafish
- Animals
- Neoplasm Metastasis
- Gene Expression Regulation, Neoplastic
- Humans
- Colorectal Neoplasms*/genetics
- Colorectal Neoplasms*/metabolism
- Colorectal Neoplasms*/pathology
- Cytosine*/analogs & derivatives
- Cytosine*/metabolism
- Liver Neoplasms*/genetics
- Liver Neoplasms*/metabolism
- Liver Neoplasms*/secondary
- PubMed
- 40241172 Full text @ BMC Biol.
Citation
Murcott, B., Honig, F., Halliwell, D.O., Tian, Y., Robson, J.L., Manasterski, P., Pinnell, J., Dix-Peek, T., Uribe-Lewis, S., Ibrahim, A.E.K., Sero, J., Gurevich, D., Nikolaou, N., Murrell, A. (2025) Colorectal cancer progression to metastasis is associated with dynamic genome-wide biphasic 5-hydroxymethylcytosine accumulation. BMC Biology. 23:100100.
Abstract
Background Colorectal cancer (CRC) progression from adenoma to adenocarcinoma is associated with global reduction in 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). DNA hypomethylation continues upon liver metastasis. Here we examine 5hmC changes upon progression to liver metastasis.
Results 5hmC is increased in metastatic liver tissue relative to the primary colon tumour and expression of TET2 and TET3 is negatively correlated with risk for metastasis in patients with CRC. Genes associated with increased 5-hydroxymethylcytosine show KEGG enrichment for adherens junctions, cytoskeleton and cell migration around a core cadherin (CDH2) network. Overall, the 5-hydroxymethylcyosine profile in the liver metastasis is similar to normal colon appearing to recover at many loci where it was originally present in normal colon and then spreading to adjacent sites. The underlying sequences at the recover and spread regions are enriched for SALL4, ZNF770, ZNF121 and PAX5 transcription factor binding sites. Finally, we show in a zebrafish migration assay using SW480 CRISPR-engineered TET knockout and rescue cells that reduced TET expression leads to a reduced migration frequency.
Conclusions Together these results suggest a biphasic trajectory for 5-hydroxymethyation dynamics that has bearing on potential therapeutic interventions aimed at manipulating 5-hydroxymethylcytosine levels.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping