We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
DNA Methylation-Mediated Downregulation of DEFB1 in Prostate Cancer Cells.
- Authors
Lee, Jaehyouk; Han, Jun Hyun; Jang, Ara; Kim, Jin Wook; Hong, Soon Auck; Myung, Soon Chul
- Abstract
Epigenetic aberrations play crucial roles in prostate cancer (PCa) development and progression. The DEFB1 gene, which encodes human ß-defensin-1 (HBD-1), contributes to innate immune responses and functions as a potential tumor suppressor in urological cancers. We investigated whether differential DNA methylation at the low CpG-content promoter (LCP) of DEFB1 was associated with transcriptional regulation of DEFB1 in PCa cells. To identify distinct CpG loci within the DEFB1 LCP related to the epigenetic regulation of DEFB1, we performed an in vitro methylated reporter assay followed by bisulfite sequencing of the DEFB1 promoter fragment. The methylation status of two adjacent CpG loci in the DEFB1 LCP was found to be important for DEFB1 expression in PCa cells. Paired epithelial specimens of PCa patients (n = 60), which were distinguished as non-tumor and tumor tissues by microdissection, were analyzed by bisulfite pyrosequencing of site-specific CpG dinucleotide units in the DEFB1 LCP. CpG methylation frequencies in the DEFB1 LCP were significantly higher in malignant tissues than in adjacent benign tissues across almost all PCa patients. These results suggested that methylation status of each CpG site in the DEFB1 promoter could mediate downregulation of DEFB1 in PCa cells.
- Subjects
DNA methylation; PROSTATE cancer; CANCER cells; EPIGENETICS; CANCER invasiveness; DEFENSINS
- Publication
PLoS ONE, 2016, Vol 11, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0166664