DNA Methylation-Mediated Downregulation of DEFB1 in Prostate Cancer Cells.
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.
Department of Urology, Chung-Ang University College of Medicine, Seoul 06974, Republic of Korea.|Advanced Urogenital Diseases Research Center, Chung-Ang University College of Medicine, Seoul 06974, Republic of Korea.|Bio-Integration Research Center for Nutra-Pharmaceutical Epigenetics, Chung-Ang University, Seoul 06974, Republic of Korea.
Jaehyouk
J
Lee
Department of Urology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si 18450, Republic of Korea.
Jun Hyun
JH
Han
Department of Urology, Chung-Ang University College of Medicine, Seoul 06974, Republic of Korea.|Advanced Urogenital Diseases Research Center, Chung-Ang University College of Medicine, Seoul 06974, Republic of Korea.|Bio-Integration Research Center for Nutra-Pharmaceutical Epigenetics, Chung-Ang University, Seoul 06974, Republic of Korea.
Ara
A
Jang
Bio-Integration Research Center for Nutra-Pharmaceutical Epigenetics, Chung-Ang University, Seoul 06974, Republic of Korea.
Jin Wook
JW
Kim
Department of Pathology, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea.
Soon Auck
SA
Hong
Department of Urology, Chung-Ang University College of Medicine, Seoul 06974, Republic of Korea.|Advanced Urogenital Diseases Research Center, Chung-Ang University College of Medicine, Seoul 06974, Republic of Korea.|Bio-Integration Research Center for Nutra-Pharmaceutical Epigenetics, Chung-Ang University, Seoul 06974, Republic of Korea.
Soon Chul
SC
Myung
D002460:Cell Line; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism
C406407:DEFB1 protein, human; D023083:beta-Defensins