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Research Paper|Volume 8, Issue 5|pp 933—940

MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma

Luca Falzone1, Rossella Salemi1, Salvatore Travali1, Aurora Scalisi2, James A. A. McCubrey3, Saverio Candido1, Massimo Libra1
  • 1Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology & Functional Genomics, Section of General & Clinical Pathology and Oncology, University of Catania, 95124, Catania, Italy
  • 2Oncological Pathology Unit, ASP, Catania, Italy
  • 3Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
* Co-last authors
Received: March 16, 2016Accepted: April 19, 2016Published: April 25, 2016
https://doi.org/10.18632/aging.100951

Copyright: © 2016 Falzone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 of MMP9 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.