DNA Methylation-Mediated Downregulation of DEFB1 in Prostate Cancer Cells

Lee, Jaehyouk; Han, Jun Hyun; Jang, Ara; Kim, Jin Wook; Hong, Soon Auck; Myung, Soon Chul

doi:10.1371/journal.pone.0166664

Cited by 15 publications

(13 citation statements)

References 34 publications

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“…A summary of most recent studies addressing combination strategies between epigenetics and immune environment in PCa is depicted in Table 3 [108,[141][142][143][144][145][146][147][148][149][150][151][152]. Some studies have focused on epigenetic regulation of response to IFN, where both methylation and acetylation can be involved, as demonstrated by Dunn and collaborators [141].…”

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

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Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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“…Both protein and mRNA levels of EBNA1BP2 were reported to be upregulated in lung cancer samples. EBNA1BP2 may promote cancer cell proliferation by blocking the degradation of oncogene c-Myc [ 43 ]. lncRNA DLG5-AS1 may be a newly identified biomarker and therapeutic target for cancer because there was no evidence to show its association with cancer.…”

Section: Discussionmentioning

confidence: 99%

Coexpression Network Analysis Identifies a Novel Nine-RNA Signature to Improve Prognostic Prediction for Prostate Cancer Patients

Cai

Chen

et al. 2020

BioMed Research International

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Background. Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer death in men. Recent studies suggest the molecular signature was more effective than the clinical indicators for the prognostic prediction, but all of the known studies focused on a single RNA type. The present study was to develop a new prognostic signature by integrating long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) and evaluate its prognostic performance. Methods. The RNA expression data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) or Gene Expression Omnibus database (GSE17951, GSE7076, and GSE16560). The PCa-driven modules were identified by constructing a weighted gene coexpression network, the corresponding genes of which were overlapped with differentially expressed RNAs (DERs) screened by the MetaDE package. The optimal prognostic signature was screened using the least absolute shrinkage and selection operator analysis. The prognostic performance and functions of the combined prognostic signature was then assessed. Results. Twelve PCa-driven modules were identified using TCGA dataset and validated in the GSE17951 and GSE7076 datasets, and six of them were considered to be preserved. A total of 217 genes in these 6 modules were overlapped with 699 DERs, from which a nine-gene prognostic signature was identified (including 3 lncRNAs and 6 mRNAs), and the risk score of each patient was calculated. The overall survival was significantly shortened in patients having the risk score higher than the cut-off, which was demonstrated in TCGA (p=5.063E−03) dataset and validated in the GSE16560 (p=3.268E−02) dataset. The prediction accuracy of this risk score was higher than that of clinical indicators (the Gleason score and prostate-specific antigen) or the single RNA type, with the area under the receiver operator characteristic curve of 0.945. Besides, some new therapeutic targets and mechanisms (MAGI2-AS3-SPARC/GJA1/CYSLTR1, DLG5-AS1-DEFB1, and RHPN1-AS1-CDC45/ORC) were also revealed. Conclusion. The risk score system established in this study may provide a novel reliable method to identify PCa patients at a high risk of death.

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“…As described in detail previously 25 , total RNA was isolated from the cell lines using the RNeasy Mini Kit (Qiagen) following the manufacturer's instructions. cDNA synthesis for real-time two-step reverse transcription polymerase chain reaction (PCR) was performed on 1 µg of total RNA using the QuantiTect Reverse Transcription Kit (Qiagen), and then 1 µl of diluted cDNA was utilized for cycling reactions using the Rotor-Gene SYBR Green PCR Kit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

Epigenetic Regulation of Filaggrin Gene Expression in Human Epidermal Keratinocytes

et al. 2020

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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. Methods Quantitative polymerase chain reaction was performed to determine the restoration of FLG mRNA expression in normal human epidermal keratinocyte (NHEK) cells after treatment with epigenetic modulating agents. Bisulfite genomic sequencing and pyrosequencing analyses of the FLG promoter region were conducted to identify the citical CpG sites relevant to FLG expression. We performed small-scale pilot study for epidermal tissues obtained from Korean patients with severe AD. Results We here show that DNA methylation in the FLG with non-CpG island promoter is responsible for the transcriptional regulation of FLG in undifferentiated NHEK cells. The methylation frequencies in a single CpG site of the FLG promoter were significantly higher in lesional epidermis than those in matched nonlesional epidermis of subjects with severe AD. Conclusion Our in vitro and clinical studies point to this unique CpG site as a potential DNA methylation marker of FLG, which can be a promising therapeutic target in the complications of filaggrin-related skin barrier dysfunction as well as in AD.

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DNA Methylation-Mediated Downregulation of DEFB1 in Prostate Cancer Cells

Cited by 15 publications

References 34 publications

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Coexpression Network Analysis Identifies a Novel Nine-RNA Signature to Improve Prognostic Prediction for Prostate Cancer Patients

Epigenetic Regulation of Filaggrin Gene Expression in Human Epidermal Keratinocytes

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