Heterogeneity of DNA methylation in multifocal prostate cancer

Serenaite, Inga; Daniūnaitė, Kristina; Jankevičius, Feliksas; Laurinavičius, Arvydas; Petroška, Donatas; Lazutka, Juozas R.; Jarmalaitė, Sonata

doi:10.1007/s00428-014-1678-3

Cited by 10 publications

(7 citation statements)

References 29 publications

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“…CpG methylation functions as an important regulatory factor in the control of gene expression . Several studies reported that promoter hypermethylation affects the regulation of ESR1 gene expression in many cancers, such as breast cancer, squamous cell cervical cancer, prostate cancer, and osteosarcoma . As shown in Supporting Information Figure S4A‐B, the MethHc database showed that ESR1 had high DNA methylation levels, and its DNA methylation was negatively correlated with ESR1 mRNA expression levels in BCa.…”

Section: Resultsmentioning

confidence: 99%

miR‐4324‐RACGAP1‐STAT3‐ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer

Lü

et al. 2019

Intl Journal of Cancer

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Considering the importance of microRNAs (miRNAs) in regulating cellular processes, we performed microarray analysis and revealed miR‐4324 as one of the most differentially expressed miRNAs in bladder cancer (BCa). Then, we discovered that miR‐4324 was a negative regulator of Rac GTPase activating protein 1 (RACGAP1) and that RACGAP1 functioned as an oncogenic protein in BCa. Our studies indicated that ectopic overexpression of miR‐4324 in BCa cells significantly suppressed cell proliferation and metastasis and enhanced chemotherapy sensitivity to doxorubicin by repressing RACGAP1 expression. Further studies showed that estrogen receptor 1 (ESR1) increased the expression of miR‐4324 by binding to its promoter, while the downregulation of ESR1 in BCa was caused by hypermethylation of its promoter. p‐STAT3 induced the enrichment of DNMT3B by binding to the ESR1 promoter and then induced methylation of the ESR1 promoter. In turn, RACGAP1 induced STAT3 phosphorylation, increasing p‐STAT3 expression and promoting its translocation to the nucleus. Therefore, the miR‐4324‐RACGAP1‐STAT3‐ESR1 feedback loop could be a critical regulator of BCa progression.

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Section: Resultsmentioning

confidence: 99%

miR‐4324‐RACGAP1‐STAT3‐ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer

Lü

et al. 2019

Intl Journal of Cancer

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“…For example, reflecting the work of Huggins, the role of ERα and ERβ signaling in the prostate have been re-investigated and distortions to expression of these receptors appears important(68–70). Similarly, an appreciation has emerged of the importance of AR signaling in tissues other than the prostate, notably in breast cancer(71, 72).…”

Section: Introductionmentioning

confidence: 99%

Pan-Cancer Analyses of the Nuclear Receptor Superfamily

Long

Campbell

2015

Nuclear Receptor Research

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Nuclear receptors (NR) act as an integrated conduit for environmental and hormonal signals to govern genomic responses, which relate to cell fate decisions. We review how their integrated actions with each other, shared co-factors and other transcription factors are disrupted in cancer. Steroid hormone nuclear receptors are oncogenic drivers in breast and prostate cancer and blockade of signaling is a major therapeutic goal. By contrast to blockade of receptors, in other cancers enhanced receptor function is attractive, as illustrated initially with targeting of retinoic acid receptors in leukemia. In the post-genomic era large consortia, such as The Cancer Genome Atlas, have developed a remarkable volume of genomic data with which to examine multiple aspects of nuclear receptor status in a pan-cancer manner. Therefore to extend the review of NR function we have also undertaken bioinformatics analyses of NR expression in over 3000 tumors, spread across six different tumor types (bladder, breast, colon, head and neck, liver and prostate). Specifically, to ask how the NR expression was distorted (altered expression, mutation and CNV) we have applied bootstrapping approaches to simulate data for comparison, and also compared these NR findings to 12 other transcription factor families. Nuclear receptors were uniquely and uniformly downregulated across all six tumor types, more than predicted by chance. These approaches also revealed that each tumor type had a specific NR expression profile but these were most similar between breast and prostate cancer. Some NRs were down-regulated in at least five tumor types (e.g. NR3C2/MR and NR5A2/LRH-1)) whereas others were uniquely down-regulated in one tumor (e.g. NR1B3/RARG). The downregulation was not driven by copy number variation or mutation and epigenetic mechanisms maybe responsible for the altered nuclear receptor expression.

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“…For DNA methylation assessment, the pairs of primers specific to methylated (M) and unmethylated (U) sequences within the 5‘region of P14 , P16 , MGMT, RARB, RASSF1, DAPK1, GSTP1, ESR1 (two 5′ regions of the ESR1 gene, one in promoter region and one intragenic sequence, were included into this study and marked as ESR1-1 and ESR1-4 , respectively), PRKCB, MT1E, MT1F, MT1G, APC, ADAMTS12 , and RUNX3. Genes were designed using Methyl Primer Express v1.0 software (Applied Biosystems (ABI), TFS) or selected based on BC specificity and diagnostic and/or outcome prediction capabilities from our previous studies [ 27 , 28 , 29 ] (see Supplementary Table S3 ). Methylation-specific PCR (MSP) mix of the final volume of 25 µL contained 10 ng of bisulfite-modified DNA template, PCR buffer, 1.6 mM of each dNTP, 2.5 mM of MgCl2, 1 µM of each primer, enhancer, and 0.5 U of Gold polymerase (ABI, TFS).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Intrinsic Breast Cancer Subtypes: The Clinical Utility of Epigenetic Biomarkers and TP53 Mutation Status in Triple-Negative Cases

Sadzevičienė

Snipaitiene

Scesnaite-Jerdiakova

et al. 2022

IJMS

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This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 control noncancerous cases. At least one gene methylation was detected in all BC specimens and a 10-gene panel statistically significantly separated tumors from noncancerous breast tissues. Methylation of FILIP1L and MT1E was predominant in triple-negative (TN) BC, while other BC subtypes were characterized by RASSF1, PRKCB, MT1G, APC, and RUNX3 hypermethylation. TP53 mutation (TP53-mut) was found in 38% of sequenced samples and mainly affected TN BC cases (87%). Cox analysis revealed that TN status, age at diagnosis, and RUNX3 methylation are independent prognostic factors for overall survival (OS) in BC. The combinations of methylated biomarkers, RUNX3 with MT1E or FILIP1L, were also predictive for shorter OS, whereas methylated FILIP1L was predictive of a poor outcome in the TP53-mut subgroup. Therefore, DNA methylation patterns of specific genes significantly separate BC from noncancerous breast tissues and distinguishes TN cases from non-TN BC, whereas the combination of two-to-three epigenetic biomarkers can be an informative tool for BC outcome predictions.

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Heterogeneity of DNA methylation in multifocal prostate cancer

Cited by 10 publications

References 29 publications

miR‐4324‐RACGAP1‐STAT3‐ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer

miR‐4324‐RACGAP1‐STAT3‐ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer

Pan-Cancer Analyses of the Nuclear Receptor Superfamily

Analysis of Intrinsic Breast Cancer Subtypes: The Clinical Utility of Epigenetic Biomarkers and TP53 Mutation Status in Triple-Negative Cases

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