Epigenetic dysregulation of H19/IGF2 in hepatic cells exposed to toxic metal mixtures in vitro.

Exposure to mixtures of toxic metals is known to cause adverse health effects through epigenetic alterations. Here we aimed to examine the unexplored area of aberrant DNA methylation in the H19/IGF2 domain following combined toxic metal exposure. An in vitro epigenotoxicity assay using the human normal liver epithelial cell line THLE-3 was conducted.

Epigenetic Regulation of Filaggrin Gene Expression in Human Epidermal Keratinocytes.

Background: Loss-of-function mutations in the filaggrin gene (FLG), which encodes an epidermal protein crucial for the formation of a functional skin barrier, have been identified as a major predisposing factor in the etiopathogenesis of atopic dermatitis (AD). Recent reports of relatively low frequencies of FLG-null mutations among specific ethnic groups with AD necessitated analysis of the epigenetic regulation which may control FLG expression without altering its DNA sequence.

Objective: The study aimed to identify DNA methylation-dependent regulation of FLG expression.

Adipogenic effects of prenatal exposure to bisphenol S (BPS) in adult F1 male mice.

Bisphenol S (BPS) has been increasingly used as a substitute for bisphenol A (BPA), a known endocrine disruptor. Early-life exposure to BPA affects fetal development and the risk of obesity in adolescence and adulthood. However, the effects of fetal exposure BPS in later life are unknown.

Promoter DNA methylation contributes to human -defensin-1 deficiency in atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by epidermal barrier dysfunction and dysregulation of innate and adaptive immunity. Epigenetic regulation of human -defensin-1 (HBD-1) might be associated with a variety of defects in the innate immune system during AD pathogenesis. We investigated the possible mechanism of decreased gene expression in AD and demonstrated the restoration of HBD-1 transcription in undifferentiated normal human epidermal keratinocyte cells after treatment with a DNA methyltransferase inhibitor.

Epigenetic suppression of the anti-aging gene in human prostate cancer cell lines.

was originally identified as an aging-suppressor gene that causes a human aging-like phenotype when tested in -deficient-mice. Recent evidence suggests that functions as a tumor suppressor by inhibiting signaling. gene silencing, including DNA methylation, has been observed in some human cancers.

Distinct Histone Modifications Modulate DEFB1 Expression in Human Vaginal Keratinocytes in Response to Lactobacillus spp.

Vaginal commensal lactobacilli are considered to contribute significantly to the control of vaginal microbiota by competing with other microflora for adherence to the vaginal epithelium and by producing antimicrobial compounds. However, the molecular mechanisms of symbiotic prokaryotic-eukaryotic communication in the vaginal ecosystem remain poorly understood. Here, we showed that both DNA methylation and histone modifications were associated with expression of the DEFB1 gene, which encodes the antimicrobial peptide human β-defensin-1, in vaginal keratinocyte VK2/E6E7 cells.

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.

Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells.

Previously, using the Illumina HumanHT-12 microarray we found that β-defensin 131 (DEFB131), an antimicrobial peptide, is upregulated in the human prostate epithelial cell line RWPE-1 upon stimulation with lipoteichoic acid (LTA; a gram-positive bacterial component), than that in the untreated RWPE-1 cells. In the current study, we aimed to investigate the role of DEFB131 in RWPE-1 cells during bacterial infection. We examined the intracellular signaling pathways and nuclear responses in RWPE-1 cells that contribute to DEFB131 gene induction upon stimulation with LTA.

The association between KL polymorphism and prostate cancer risk in Korean patients.

The Klotho (KL) gene is a classical "aging suppressor" gene. Although recent studies have shown that KL participates in the progression of several types of human cancers, the relationship between KL polymorphism and prostate cancer was unknown. The present study aimed to investigate the association between KL genetic polymorphisms and prostate cancer.

Beta-Defensin 124 Is Required for Efficient Innate Immune Responses in Prostate Epithelial RWPE-1 Cells.

Purpose: The present study aimed to determine the role played by β-defensin 124 (DEFB124) in the innate immunity of prostate epithelial RWPE-1 cells during bacterial infection.

Materials And Methods: The expression of DEFB124 was examined by quantitative real-time polymerase chain reaction (PCR), Western blotting, and immunocytochemistry. Enzyme-linked immunosorbent assays and quantitative real-time PCR were performed to determine the production of cytokines and chemokines.

Single nucleotide polymorphisms in fibroblast growth factor 23 gene, FGF23, are associated with prostate cancer risk.

Objective: To determine whether sequence variants within the FGF23 gene are associated with the risk of developing prostate cancer in a Korean population.

Patients And Methods: Five common single nucleotide polymorphisms (SNPs) in the FGF23 gene were assessed in 272 patients with prostate cancer and 173 control subjects with benign prostatic hyperplasia. Single-locus analyses were conducted using conditional logistic regression.

HNF1B polymorphism associated with development of prostate cancer in Korean patients.

Objective: To identify whether the genetic variations in HNF1B are associated with the development of prostate cancer in Korean patients. Genome-wide association studies have found the HNF1B gene at 17q12 to be a major causal gene for the risk of prostate cancer.

Methods: We evaluated the association of 47 single nucleotide polymorphisms (SNPs) in the HNF1B gene with prostate cancer risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects) using unconditional logistic regression analysis.

Sequence variants of Toll-like receptor 4 (TLR4) and the risk of prostate cancer in Korean men.

Purpose: Chronic inflammation has been considered a potential risk factor for prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross talk between innate immunity and adaptive immunity. In this study, sequence variants in the TLR4 gene were investigated to determine whether they were associated with prostate cancer risk in a Korean cohort.

Epigenetic regulation of the potential tumor suppressor gene, hLHX6.1, in human cervical cancer.

It is well known that the Homo sapiens LIM homeobox domain 6 gene (hLHX6), a putative transcription regulator, controls the differentiation and development of neural and lymphoid cells, particularly in the central nervous system. In this study, we investigated hLHX6.1 (an isoform of hLHX6), which functions as a tumor suppressor gene in the cervix.

The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma.

Background: Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies.

The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer.

The homo sapiens LIM homeobox domain LHX6 gene, hLHX6, is a putative transcription regulator with homeo-domain. Multiple cytosine guanine dinucleotides (CpG island) are found in the genomic sequences between exon 4a and exon 5 of the gene encoding hLHX6s (alternative short iso-form of hLHX6 gene). This specific CpG island, hLHX6-HMR, is found frequently hypermethylated in 7 cervical cancer cell lines as shown in MSP, BSP, and COBRA assays.

Epigenetic silencing of the WNT antagonist DICKKOPF-1 in cervical cancer cell lines.

Objective: Our study was designed to demonstrate that DICKKOPF-1 (DKK-1), encoding a secreted Wnt antagonist, is transcriptionally repressed by epigenetic alterations in cervical carcinoma cell lines.

Methods: Methylation-specific PCR for 8 human cervical cancer cell lines and bisulfite sequencing for 4 cell lines exhibiting significant difference in methylation levels were used to determine CpG-island methylation status at the 5'-end region of DKK-1. The chromatin immunoprecipitation assay was performed to determine whether HeLa cells recruit histone deacetylation for DKK-1 silencing.

A new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A, activates hepatitis B virus replication.

A new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A (9-HCA-A), showed potential for activating hepatitis B virus (HBV) replication. To define the mechanism of 9-HCA-A, we used HepG2 2.