Treatment of prostate cancer cells with S-adenosylmethionine leads to genome-wide alterations in transcription profiles.
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.
Institute of Anatomy and Clinical Morphology, University of Witten/Herdecke, 58448 Witten, Germany. Electronic address: tho.h.schmidt@web.de.
Thomas
T
Schmidt
Department of Medical Statistics, University Medical Center, Goettingen, 37073 Goettingen, Germany.
Andreas
A
Leha
Department of Developmental Biochemistry, University of Goettingen, 37073 Goettingen, Germany.
Gabriela
G
Salinas-Riester
D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015894:Genome, Human / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D017423:Sequence Analysis, RNA / Q000379:methods; D013447:Sulfites; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013447:Sulfites; D012436:S-Adenosylmethionine; C042345:hydrogen sulfite
Hypomethylation; Methylome; Prostate cancer; Reduced representation bisulfite sequencing