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Angiogenin contributes to bladder cancer tumorigenesis by DNMT3b-mediated MMP2 activation

Rafael Peres1, Hideki Furuya1, Ian Pagano2

  • 1University of Hawaii Cancer Center, Clinical & Translational Research Program, Honolulu, HI, USA.

Oncotarget
|June 19, 2016
PubMed

Insights

Angiogenin (ANG) activates matrix metalloproteinase-2 (MMP2) by altering DNA methylation, promoting human tumorigenesis. This mechanism involves downregulating DNA methyltransferase 3b (DNMT3b), impacting cancer patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Epigenetics

Background:

  • Epigenetic gene regulation is critical in human cancer development.
  • Previous research identified an interplay between Angiogenin (ANG) and matrix metalloproteinase-2 (MMP2) in tumorigenesis.

Purpose of the Study:

  • To elucidate the oncogenic potential of ANG and its mechanism in human cancer.
  • To investigate the role of ANG in regulating MMP2 expression and its epigenetic modifications.

Main Methods:

  • DNA methylation microarray analysis.
  • Gene expression analysis of ANG, MMP2, and DNMT3b.
  • Assessment of DNMT3b activity and promoter recruitment.

Main Results:

  • ANG expression led to hypomethylation and increased expression of the MMP2 gene.
  • ANG manipulation affected cell migration, angiogenesis, and tumor suppressor gene pathways.
  • ANG negatively regulated DNMT3b expression and activity, inhibiting its binding to the MMP2 promoter.
  • ANG overexpression and MMP2 overexpression, along with DNMT3b underexpression, correlated with reduced disease-free survival in bladder cancer patients.

Conclusions:

  • ANG functions as an oncoprotein by activating MMP2 through epigenetic mechanisms.
  • ANG contributes to oncogenesis by modulating DNMT3b activity, leading to MMP2 activation.
  • The ANG-MMP2 pathway and DNMT3b levels serve as potential prognostic markers for human bladder cancer.
Keywords:
DNMT3bMMP2angiogeninbladder cancer

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