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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Down-regulation of DNMT3b in PC3 cells effects locus-specific DNA methylation, and represses cellular growth and

Ahmed Yaqinuddin1, Sohail A Qureshi, Romena Qazi

  • 1Department of Biological & Biomedical Sciences, The Aga Khan University, Stadium Road, Karachi 74800, Pakistan. ahmed.yaqin@aku.edu

Cancer Cell International
|September 19, 2008
PubMed
Abstract

Insights

DNA methyltransferase 3B (DNMT3b) depletion in prostate cancer cells increases apoptosis and reduces cell migration. Silencing DNMT3b also leads to hypomethylation of key gene promoters and altered gene expression.

Area of Science:

  • Epigenetics and Cancer Biology
  • Molecular Oncology

Background:

  • Aberrant DNA methylation patterns are linked to neoplasia and altered gene expression.
  • DNA methyltransferases (DNMTs) regulate methylation; DNMT3b acts as a de novo enzyme.
  • DNMT3b's role in gene-specific methylation, beyond pericentric heterochromatin, is under investigation.

Purpose of the Study:

  • To investigate the role of DNMT3b in gene-specific methylation.
  • To examine cellular and gene expression changes following DNMT3b silencing in PC3 prostate cancer cells.

Main Methods:

  • RNA interference (RNAi) was used to silence DNMT3b expression in PC3 cells.
  • Cellular changes (apoptosis, migration, invasion) were assessed.
  • Gene promoter methylation and expression profiles were analyzed.

Main Results:

  • DNMT3b depletion increased apoptosis and reduced PC3 cell migration.
  • Hypomethylation of retinoblastoma (Rb), RAR-beta, and APC gene promoters was observed.
  • CDKN3 and cytochrome b5 expression increased, while growth and invasion showed no significant change.

Conclusions:

  • DNMT3b preferentially targets specific gene promoters in PC3 cells.
  • DNMT3b depletion significantly impairs prostate cancer cell growth and migration.

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