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The up-stream regulation of polymerase-1 and transcript release factor(PTRF/Cavin-1) in prostate cancer: an epigenetic analysis

Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand

Topical Section: Molecular Research in Prostate Cancer

The expression of PTRF is down-regulated in prostate cell lines and tissues. Restorationof PTRF expression leads to a reduction in aggressive phenotypes of prostate cancer cells both in vitro and in vivo. Epigenetics examines the changes in gene expression that occur without changing DNA sequences. Two main epigenetic mechanisms include hypermethylation of the gene’s promoter region and changes to the chromatin structure through histone modification. We investigated the involvement of possible epigenetic up-stream regulatory mechanisms that may down-regulate PTRF in prostate cancer cells. Normal (RWPE-1) and prostate cancer (LNCaP and PC3) cell lines were treated with DNA methylation inhibitor, 5-aza-2Ꞌ-deoxycytidine (5AZA) and histone deacetylase inhibitor, Trichostatin-A (TSA) either independently or in combination. A bioinformatics approach was also used to investigate the changes of epigenetic driver genes in silico. In normal prostate cells(RWPE-1), and androgen independent prostate cancer cells (PC3), treatment with 5AZA and/or TSA did not affect PTRF expression. However, TSA and TSA + 5AZA treatments, but not 5AZA alone,up-regulated the expression of PTRF in LNCaP cells. Bioinformatic analysis of the potential histone deacetylase (HDAC) genes involved showed that HDAC2HDAC6 and HDAC10 may be potential candidate genes for the regulation of PTRF. This corroborative study describes the possible role of an epigenetic mechanism onPTRF, further studies are required to allow a better understanding of theup-stream mechanisms that regulate PTRF expression.
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Keywords DNA methylation; histone deacetylase; histone modification

Citation: Jin-Yih Low, Helen D. Nicholson. The up-stream regulation of polymerase-1 and transcript release factor(PTRF/Cavin-1) in prostate cancer: an epigenetic analysis. AIMS Molecular Science, 2016, 3(3): 466-478. doi: 10.3934/molsci.2016.3.466


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