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Promoter hypermethylation of membrane type 3 matrix metalloproteinase is associated with cell migration in colorectal adenocarcinoma.

Abstract
The gene MT3-MMP (also known as MMP16) encodes the membrane type 3 matrix metalloproteinase, which is a member of the matrix metalloproteinase (MMP) gene family. Several MMPs are associated with migration in colorectal cancer (CRC). However, the methylation status of the MT3-MMP promoter in CRC has not been reported. The methylation status and expression levels of MT3-MMP were investigated in primary tumor tissues and adjacent normal tissues in 105 patients with CRC, one normal colon cell line (CCD18Co), and three CRC cell lines (SW480, DLD-1, and LoVo) by quantitative methylation-specific PCR and real-time PCR. MT3-MMP was hypermethylated in 82 of 105 CRC tissues (78%), 30 of 105 adjacent normal tissues (29%), and two of 11 normal colon tissues (18%). MT3-MMP mRNA was significantly reduced in CRC compared with that in adjacent normal tissues (P < 0.05). The methylation-mediated downregulation of MT3-MMP was restored by treatment with 5-aza-2'-deoxycytidine in two CRC cell lines, and MT3-MMP promoter activity was significantly reduced by methylation. The knockdown of MT3-MMP induced cell migration, but overexpressed MT3-MMP reduced cell migration in CRC cells. These results demonstrate that the MT3-MMP promoter is frequently hypermethylated in CRC and that downregulation of MT3-MMP may be important for cell migration in CRC.
AuthorsJi Wook Moon, Jong-Ho Choi, Soo Kyung Lee, Yong Woo Lee, Jung Ok Lee, Nami Kim, Hye Jeong Lee, Jung Seon Seo, Jin Kim, Hyeon Soo Kim, Gi Jin Kim, Sun-Hwa Park
JournalCancer genetics (Cancer Genet) Vol. 208 Issue 5 Pg. 261-70 (May 2015) ISSN: 2210-7762 [Print] United States
PMID26002729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • MMP16 protein, human
  • RNA, Small Interfering
  • Decitabine
  • Matrix Metalloproteinase 16
  • Azacitidine
Topics
  • Adenocarcinoma (genetics, pathology)
  • Aged
  • Azacitidine (analogs & derivatives, pharmacology)
  • Cell Line, Tumor
  • Cell Movement (genetics)
  • Colorectal Neoplasms (genetics, pathology)
  • DNA Methylation (genetics)
  • Decitabine
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matrix Metalloproteinase 16 (biosynthesis, genetics)
  • Promoter Regions, Genetic (genetics)
  • RNA Interference
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction

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