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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
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TET2 Negatively Regulates Nestin Expression in Human Melanoma
Camilla B F Gomes1, Karina G Zechin2, Shuyun Xu3
1Program in Oral Pathology, Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, Brazil; Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
The American Journal of Pathology
|April 23, 2016
Summary
Loss of ten-eleven translocation methylcytosine dioxygenase (TET2)-mediated 5-hydroxymethylcytosine (5-hmC) drives melanoma growth. This study reveals TET2 epigenetically regulates nestin via 5-hmC, impacting melanoma virulence.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Melanoma virulence pathways are not fully understood.
- Ten-eleven translocation methylcytosine dioxygenase (TET2) and 5-hydroxymethylcytosine (5-hmC) are implicated in melanoma.
- Nestin protein correlates with melanoma tumorigenesis and invasion.
Purpose of the Study:
- To investigate the relationship between TET2-mediated 5-hmC and nestin in melanoma.
- To elucidate the epigenetic regulation of nestin by TET2 in melanoma.
Main Methods:
- Immunohistochemistry on patient melanoma samples.
- In vitro studies with human melanoma cell lines.
- Genome-wide mapping using hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq).
Main Results:
- A significant negative correlation was observed between nestin and 5-hmC levels in melanoma.
- Restoring 5-hmC reduced nestin gene and protein expression in vitro.
- 5-hmC binding at the nestin gene's 3' untranslated region was decreased in melanoma and increased upon TET2 overexpression.
Conclusions:
- TET2 epigenetically regulates nestin expression via 5-hmC binding at the nestin gene's 3' UTR.
- This pathway offers a potential explanation for melanoma growth and virulence.
- Further studies are needed to define the interplay between 5-hmC, nestin, and melanoma virulence.
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