Treatment of prostate cancer cells with S-adenosylmethionine leads to genome-wide alterations in transcription profiles

Gene. 2016 Dec 31;595(2):161-167. doi: 10.1016/j.gene.2016.09.032. Epub 2016 Sep 26.

Abstract

The hypomethylation of DNA may support tumor progression; however, the mechanism underlying this relationship is not clear. Several studies have demonstrated that the in vitro application of the methyl donor S-adenosylmethionine (SAM) leads to promoter remethylation and the downregulation of proto-oncogene expression in cancer cells. It is not clear if this represents a general mechanism of SAM or is limited to selected genes. We examined this problem using new bisulfite sequencing and transcriptomic technologies. Treatment with SAM caused the downregulation of proliferation, migration, and invasion of prostate cancer (PC-3) cells. RNA sequencing revealed the genome-wide downregulation of genes involved in proliferation, migration, invasion, and angiogenesis. Real-time PCR of a subset of the genes confirmed these results. Reduced representation bisulfite sequencing (RRBS) displayed only minor differential methylation between treated cells and controls. In summary, we confirmed the anti-proliferative and anti-invasive effects of SAM. Additionally, we observed anti-migratory effects and downregulation of genes, especially those related to cancerogenesis. For some of the related genes, this is the first reported evidence of an association with prostate cancer. However, genome-wide modifications in methylation profiles were not observed by RRBS; thus, they are obviously not a major cause of alteration in transcription profiles and anti-cancer effects.

Keywords: Hypomethylation; Methylome; Prostate cancer; Reduced representation bisulfite sequencing.

MeSH terms

  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • DNA Methylation / drug effects
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genome, Human / drug effects
  • Humans
  • Male
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • S-Adenosylmethionine / pharmacology*
  • Sequence Analysis, RNA / methods
  • Sulfites
  • Tumor Cells, Cultured

Substances

  • Sulfites
  • S-Adenosylmethionine
  • hydrogen sulfite