Silencing of MBD1 and MeCP2 in prostatecancer-derived PC3 cells produces differential gene expression profiles and cellular phenotypes

Ahmed Yaqinuddin, Farhat Abbas, Syed Z. Naqvi, Mohammad U. Bashir, Romena Qazi, Sohail A. Qureshi

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Alterations in genomic CpG methylation patterns have been found to be associated with cell transformation and neoplasia. Although it is recognized that methylation of CpG residues negatively regulates gene expression, how the various MBPs (methyl-binding proteins) contribute to this process remains elusive. To determine whether the two well characterized proteins MeCP2 (methyl-CpG-binding protein 2) and MBD1 (methyl-CpG-binding domain 1) have distinct or redundant functions, we employed RNAi (RNA interference) to silence their expression in the prostate cancer-derived PC3 cell line, and subsequently compared cell growth, invasion and migration properties of these cell lines in addition to their respective mRNA-expression profiles. Cells devoid of MeCP2 proliferated more poorly compared with MBD1-deficient cells and the parental PC3 cells. Enhanced apoptosis was observed in MeCP2-deficient cells, whereas apoptosis in parental and MBD1-deficient cells appeared to be equivalent. Boyden chamber invasion and wound-healing migration assays showed that MBD1-silenced cells were both more invasive and migratory compared with MeCP2-silenced cells. Finally, gene chip microarray analyses showed striking differences in the mRNAexpression profiles obtained from MeCP2- and MBD1-depleted cells relative to each other as well as when compared with control cells. The results of the present study suggest that MeCP2 and MBD1 silencing appear to affect cellular processes independently in vivo and that discrete sets of genes involved in cellular proliferation, apoptosis, invasion and migration are targeted by each protein.

Original languageEnglish
Pages (from-to)319-326
Number of pages8
JournalBioscience Reports
Issue number6
Publication statusPublished - Dec 2008


  • DNA methylation
  • Gene expression
  • Methyl-binding protein (MBP)
  • Methylated CpG (mCpG)
  • RNA interference (RNAi)


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