AI Article Synopsis
- PRAME and 5hmC are important biomarkers in melanoma, showing an inverse relationship where benign nevi have high 5hmC and low PRAME, while melanomas reverse this pattern.
- Research using various imaging and database analyses indicates that lower levels of 5hmC are linked to higher PRAME levels in both premalignant and malignant melanoma cells.
- The study suggests that TET2 plays a crucial role in regulating PRAME expression through DNA hydroxymethylation, highlighting the importance of epigenetic changes in melanoma development.
Article Abstract
Unlabelled: Preferentially Expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells. Analysis of TCGA and GTEx databases confirmed a negative relationship between TET2 and PRAME mRNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5' promoter in melanoma compared to nevi, suggesting a role for 5hmC in PRAME transcription. Restoring 5hmC levels via TET2 overexpression notably reduced PRAME expression in melanoma cell lines. These findings establish a function of TET2-mediated DNA hydroxymethylation in regulating PRAME expression and demonstrate epigenetic reprogramming as pivotal in melanoma tumorigenesis.
Teaser: Melanoma biomarker PRAME expression is negatively regulated epigenetically by TET2-mediated DNA hydroxymethylation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291125 | PMC |
| http://dx.doi.org/10.1101/2024.07.26.605293 | DOI Listing |
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