MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma.
Tumor spreading is associated with the degradation of extracellular matrix proteins, mediated by the overexpression of matrix metalloproteinase 9 (MMP-9). Although, such overexpression was linked to epigenetic promoter methylation, the role of intragenic methylation was not clarified yet. Melanoma was used as tumor model to investigate the relationship between the DNA intragenic methylation ofMMP9 gene and MMP-9 overexpression at transcriptional and protein levels. Computational analysis revealed DNA hypermethylation within the intragenic CpG-2 region of MMP9 gene in melanoma samples with high MMP-9 transcript levels. In vitro validation showed that CpG-2 hotspot region was hypermethylated in the A375 melanoma cell line with highest mRNA and protein levels of MMP-9, while low methylation levels were observed in the MEWO cell line where MMP-9 was undetectable. Concordant results were demonstrated in both A2058 and M14 cell lines. This correlation may give further insights on the role of MMP-9 upregulation in melanoma.
Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of Catania, 95124, Catania, Italy.
Luca
L
Falzone
Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of Catania, 95124, Catania, Italy.
Rossella
R
Salemi
Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of Catania, 95124, Catania, Italy.
Salvatore
S
Travali
Oncological Pathology Unit, ASP, Catania, Italy;.
Aurora
A
Scalisi
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
James A
JA
McCubrey
Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of Catania, 95124, Catania, Italy.
Saverio
S
Candido
Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of Catania, 95124, Catania, Italy.
Massimo
M
Libra
D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D020780:Matrix Metalloproteinase 9
MMP-9; epigenetic; intragenic; melanoma; methylation