Colorectal cancer progression to metastasis is associated with dynamic genome-wide biphasic 5-hydroxymethylcytosine accumulation

被引：0

作者：

Murcott, Ben ^{[1
]}

Honig, Floris ^{[1
]}

Halliwell, Dominic Oliver ^{[1
]}

Tian, Yuan ^{[1
,2
]}

Robson, James Lawrence ^{[3
]}

Manasterski, Piotr ^{[4
]}

Pinnell, Jennifer ^{[5
]}

Dix-Peek, Therese ^{[6
]}

Uribe-Lewis, Santiago ^{[7
]}

Ibrahim, Ashraf E. K. ^{[8
]}

Sero, Julia ^{[9
]}

Gurevich, David ^{[9
]}

Nikolaou, Nikolas ^{[10
]}

Murrell, Adele ^{[11
]}

机构：

[1] Univ Bath, Dept Life Sci, Bath BA2 7AY, Avon, England

[2] UCL, Canc Inst, 71 Huntley St, London WC1 6DD, England

[3] Univ West England, Dept Appl Sci, Bristol BS16 1QY, England

[4] Univ Edinburgh, Inst Genet & Canc, Edinburgh Canc Res Ctr, Crewe Rd, Edinburgh EH4 2XU, Scotland

[5] Publ Lib Sci, Nine Hills Rd, Cambridge CB2 1GE, England

[6] Univ Witwatersrand, Fac Hlth Sci, Dept Med, 7 York Rd, ZA-2193 Johannesburg, South Africa

[7] Royal Surrey Hosp NHS Fdn Trust, Stokes Ctr Urol, Guildford GU2 7XX, England

[8] North West Anglia Fdn Trust, Peterborough City Hosp, Bretton Gate, Peterborough PE3 9GZ, England

[9] Univ Bath, Ctr Therapeut Innovat, Dept Life Sci, Bath BA2 7AY, England

[10] Univ Exeter, Living Syst Inst, Clin & Biomed Sci, Exeter EX4 4QD, England

[11] Univ Bath, Ctr Bioengn & Biomed Technol, Ctr Math Biol, Dept Life Sci, Bath BA2 7AY, England

来源：

BMC BIOLOGY | 2025年 / 23卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

5-Hydroxymethylcytosine; Colorectal cancer progression to metastasis; Ten-eleven-translocation (TET); Epigenetics; Zebrafish assay; ISLAND METHYLATOR PHENOTYPE; DNA METHYLATION; TET PROTEINS; HEPATOCELLULAR-CARCINOMA; PROGNOSTIC-FACTOR; EXPRESSION; 5-METHYLCYTOSINE; CONVERSION; SURVIVAL; CELLS;

D O I：

10.1186/s12915-025-02205-y; 10.1186/s12915-025-02205-y

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

BackgroundColorectal 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.Results5hmC 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.ConclusionsTogether these results suggest a biphasic trajectory for 5-hydroxymethyation dynamics that has bearing on potential therapeutic interventions aimed at manipulating 5-hydroxymethylcytosine levels.

引用

页数：19

共 78 条

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