Epigenetic Modifications in Prostate Cancer

Ngollo, Marjolaine; Dagdemir, Aslihan; Karslı-Çeppioğlu, Seher; Judes, Gaëlle; Pajon, Amaury; Penault‐Llorca, Frédérique; Boiteux, Jean‐Paul; Bignon, Yves‐Jean; Guy, Laurent; Bernard‐Gallon, Dominique

doi:10.2217/epi.14.34

Cited by 44 publications

(31 citation statements)

References 80 publications

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“…Unfortunately, most of them still develop resistance, stressing that further development of medical interventions of CRPC is necessary. In the realm of PC epigenomics, extensive researches have been carried out in DNA methylation, histone modifications and microRNAs [41]. The enhancer related epigenomic studies, however, remain a gap in the field of PC research.…”

Section: Discussionmentioning

confidence: 99%

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Zhao

Wang

et al. 2016

Oncotarget

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Enzalutamide is a second-generation anti-androgen for treatment of castration-resistant prostate cancer (CPRC). It prolongs survival of CRPC patients, but its overall survival benefit is relatively modest (4.8 months) and by 24 months most patients progress on enzalutamide. To date, however, the molecular mechanisms underlying enzalutamide resistance remain elusive. Herein, we report enzalutamide treatment-induced alterations of androgen receptor (AR)-regulated enhancer RNAs (AR-eRNAs) and their roles in enzalutamide-resistant growth and survival of CRPC cells. AR chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) and RNA-seq analyses revealed that 188 and 227 AR-eRNAs were differentially expressed in enzalutamide-resistant LNCaP and C4-2 cells, respectively. The AR-eRNAs upregulated in C4-2 cells and downregulated in LNCaP cells were selected through meta-analysis. Expression of AR-eRNAs and related mRNAs in the loci of FTO, LUZP2, MARC1 and NCAM2 were further verified by real-time RT-PCR. Silencing of LUZP2 inhibited, but silencing of MARC1 increased the growth of enzalutamide-resistant C4-2 cells. Intriguingly, meta-analysis showed that expression of LUZP2 mRNA increased in primary tumors compared to normal prostate tissues, but decreased again in metastatic CRPC. Our findings suggest that eRNA alteration profiling is a viable new approach to identify functional gene loci that may not only contribute to enzalutamide-resistant growth of CRPC, but also serve as new targets for CRPC therapy.

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Section: Discussionmentioning

confidence: 99%

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Zhao

Wang

et al. 2016

Oncotarget

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“…A full discussion of epigenomics as it relates to prostate cancer and BPH is beyond the scope of this review, interested readers are directed toward several reviews on the topic [68–70]. There are numerous genes regulated by DNA methylation in prostate cancer [52,68–71].…”

Section: Prostate Cancer and Benign Prostate Hyperplasia (Bph): A Reawamentioning

confidence: 99%

DNA Methylation as a Dynamic Regulator of Development and Disease Processes: Spotlight on the Prostate

Keil

Vezina

2015

Epigenomics

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Prostate development, benign hyperplasia and cancer involve androgen and growth factor signaling as well as stromal–epithelial interactions. We review how DNA methylation influences these and related processes in other organ systems such as how proliferation is restricted to specific cell populations during defined temporal windows, how androgens elicit their actions and how cells establish, maintain and remodel DNA methylation in a time and cell specific fashion. We also discuss mechanisms by which hormones and endocrine disrupting chemicals reprogram DNA methylation in the prostate and elsewhere and examine evidence for a reawakening of developmental epigenetic pathways as drivers of prostate cancer and benign prostate hyperplasia.

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“…[5–8] DNA methylation—a major molecular mechanism of epigenetic changes—has been recognized as an important event in many cancer types, including lung cancer. [9,10] Studies have shown that gene methylation in the promoter regions regulates the silencing of tumor suppressor genes (TSGs), leading to the down-regulation of gene expression.…”

Section: Introductionmentioning

confidence: 99%

Promoter hypermethylation of Wnt inhibitory factor-1 in patients with lung cancer

Zheng

Jiang

et al. 2016

Medicine

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Background:Promoter hypermethylation of Wnt inhibitory factor-1 (WIF-1)—a tumor suppressor gene—has been detected in several types of human tumors. However, the association between WIF-1 promoter hypermethylation and lung cancer remains to be elucidated. Therefore, we conducted this study to evaluate the clinical significance of WIF-1 promoter hypermethylation in lung cancer.Methods:A comprehensive literature search was conducted to obtain eligible studies. The combined odds ratios (ORs) or hazard ratios and 95% confidence intervals were used to estimate the strength of associations.Results:A total of 8 eligible publications with 626 cases and 512 controls were included in our study. The combined ORs revealed that WIF-1 promoter hypermethylation was significantly higher in lung cancer than in controls (OR 10.53, P < 0.001). Moreover, WIF-1 promoter hypermethylation was significantly associated with smoking behavior (OR 1.88, P = 0.002). No significant correlation was found between WIF-1 promoter hypermethylation and sex status, age status, tumor stage, and pathological types in cancer. Multivariate analysis results indicated the absence of correlation between WIF-1 promoter hypermethylation and with relapse-free survival and overall survival. Subgroup analysis by sample type demonstrated that promoter hypermethylation of WIF-1 was significantly associated with an increased risk of lung cancer in the tissue (OR 7.89, P < 0.001), blood (OR 21.83, P = 0.034), and pleural effusion subgroups (OR 157.43, P = 0.001).Conclusions:Promoter hypermethylation of WIF-1 may play a crucial role in lung cancer carcinogenesis. It may be a noninvasive biomarker using blood or pleural effusion detection. WIF-1 promoter hypermethylation is correlated with smoking behavior, but not with sex status, age status, tumor stage, pathological types, and the prognosis of lung cancer patients in terms of relapse-free survival and overall survival. More investigations, including a larger number of subjects, are required to further confirm the findings of our analysis.

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Epigenetic Modifications in Prostate Cancer

Cited by 44 publications

References 80 publications

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

DNA Methylation as a Dynamic Regulator of Development and Disease Processes: Spotlight on the Prostate

Promoter hypermethylation of Wnt inhibitory factor-1 in patients with lung cancer

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